9 Matching Annotations
  1. Oct 2026
  2. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    The H Syndrome Is Caused by Mutations in the Nucleoside Transporter hENT3
    7
    1. ClingenBaseline 24 Oct 2026
      GII-3

      Case: Family G Proband GII-3, male, 13yo at report

      CasePresentingHPOs: HP:0000953, HP:0000998, HP:0030053, HP:0000054, HP:0002240, HP:0001642, HP:0000365, HP:0001822, HP:0100490, HP:0002619

      CasePresentingHPOsFreeText: subcutaneous masses in genital area, dilated lateral scleral vasculature

      CaseNOTHPOs: HP:0034373, HP:0007380, HP:0001256, HP:0000520

      CaseNOTHPOSFreeText:

      CasePreviousTesting: Direct sequencing of AIFM2, ADAMTS14, EIF4EBP2, C10ORF54, PPA1, H2AFY2, LRRC20, NODAL, PRF1, TYSND1, SAR1A, PSAP, NPFFR1, and C10ORF27

      CaseGenotypingMethod: Microarray, homozygosity mapping, haplotype analysis, direct sequencing of exons of SLC29A3, restriction digestion

      Variant: G437R homozygous

      ClinVarID: or CAID: 565/CA114352

      gnomAD: The missense variant G437R is present in gnomAD v4.0.0 with a MAF=0.00006666 (4/60002 alleles) in the Admixed American population and 0 homozygotes.

      AddCaseInfo: Female cousin, GII-10, is also affected but lacks the classical cutaneous findings

      PreviouslyPublished: n/a

      VariantEvidence: Functional characterization of G437R in Xenopus oocytes showed that transport activity was approximately half of WT SLC29A3. Studies in NIH 3T3 fibroblasts demonstrated accelerated turnover of the G437R mutant compared to WT, suggesting decreased stability (Kang et al. 2010; PMID: 20595384)

      CaseInfo Individual CA114352 ClinVarID: 565 inferred_gene_hgnc:23096 inferred_gene_source:CAID UNC Biocuration Core
    2. ClingenBaseline 24 Oct 2026
      Figure 2Haplotype Analysis Performed in Six Families with H SyndromeAffected individuals are marked by gray symbols. The disease-associated haplotypes in the linked interval on chromosome 10q21.3–q22.1 are shown by vertical bars (red and green) in families A–F. Alleles excluded by recombination events are marked in pink. The physical locations of the polymorphic microsatellites are given near the haplotype for individual AI-2.

      Case: Family A Proband AII-8, male, Arabic, Israeli, 13yo at report

      CasePresentingHPOs: HP:0000953, HP:0000998, HP:0000054, HP:0001433, HP:0011025, HP:0000365, HP:0000520, HP:0012385, HP:0001684, HP:0000823, HP:0030053, HP:0100324, HP:0100727

      CasePresentingHPOsFreeText: Scrotal masses, Dilated scleral vessels

      CaseNOTHPOs: HP:0008064, HP:0002619, HP:0007380

      CaseNOTHPOSFreeText:

      CasePreviousTesting: direct sequencing of AIFM2, ADAMTS14, EIF4EBP2, C10ORF54, PPA1, H2AFY2, LRRC20, NODAL, PRF1, TYSND1, SAR1A, PSAP, NPFFR1, and C10ORF27

      CaseGenotypingMethod: microarray, haplotype analysis, direct sequencing of exons of SLC29A3, restriction digestion

      Variant: G427S; G437R

      ClinVarID: or CAID: 563/CA114349; 565/CA114352

      gnomAD: The missense variant G427S is present in gnomAD v4.0.0 with a MAF=0.00005339 (4/74926 alleles) in the African/African American population and 0 homozygotes. The missense variant G437R is present in gnomAD v4.0.0 with a MAF=0.00006666 (4/60002 alleles) in the Admixed American population and 0 homozygotes.

      AddCaseInfo: consanguineous parents; mother was het for G427S, but father's genotype was not provided

      PreviouslyPublished: PMID: 18410979

      VariantEvidence: Functional studies in Xenopus oocytes demonstrated that G427S results in a total loss of transport activity (Kang et al. 2010; PMID: 20595384).

      Kang et al. (2010) performed functional characterization of the G437R mutation in Xenopus oocytes and observed transport activity that was approximately half that of wildtype SLC29A3. Studies in NIH 3T3 fibroblasts demonstrated accelerated turnover of the G437R mutant compared to wildtype, suggesting decreased stability.

      CaseInfo Individual CA114349 ClinVarID: 563 ClinVarID: 565 CA114352 PreviouslyPublished inferred_gene_hgnc:23096 inferred_gene_source:CAID UNC Biocuration Core
    3. ClingenBaseline 24 Oct 2026
      HII-2

      Case: Family H Proband HII-2, female, 50yo at report

      CasePresentingHPOs: HP:0000823, HP:0002240, HP:0001822, HP:0034373, HP:0100490, HP:0002619, HP:0000520, HP:0001838, HP:0007380, HP:0001084, HP:0001871, HP:0004322, HP:0000135, HP:0000141, HP:0012410, HP:0011974

      CasePresentingHPOsFreeText: stasis ulcers

      CaseNOTHPOs: HP:0000953, HP:0000998, HP:0030053, HP:0001256

      CaseNOTHPOSFreeText: dilated lateral scleral vasculature

      CasePreviousTesting: Direct sequencing of AIFM2, ADAMTS14, EIF4EBP2, C10ORF54, PPA1, H2AFY2, LRRC20, NODAL, PRF1, TYSND1, SAR1A, PSAP, NPFFR1, and C10ORF27

      CaseGenotypingMethod: Microarray, homozygosity mapping, haplotype analysis, direct sequencing of exons of SLC29A3, restriction digestion

      Variant: G437R homozygous

      ClinVarID: or CAID: 565/CA114352

      gnomAD: The missense variant G437R is present in gnomAD v4.0.0 with a MAF=0.00006666 (4/60002 alleles) in the Admixed American population and 0 homozygotes.

      AddCaseInfo: Consanguineous parents, not genotyped. 3 unaffected, not genotyped siblings

      PreviouslyPublished: n/a

      VariantEvidence: Functional characterization of G437R in Xenopus oocytes showed that transport activity was approximately half of WT SLC29A3. Studies in NIH 3T3 fibroblasts demonstrated accelerated turnover of the G437R mutant compared to WT, suggesting decreased stability (Kang et al. 2010; PMID: 20595384)

      CaseInfo Individual CA114352 ClinVarID: 565 inferred_gene_hgnc:23096 inferred_gene_source:CAID UNC Biocuration Core
    4. ClingenBaseline 23 Oct 2026
      Figure 2Haplotype Analysis Performed in Six Families with H SyndromeAffected individuals are marked by gray symbols. The disease-associated haplotypes in the linked interval on chromosome 10q21.3–q22.1 are shown by vertical bars (red and green) in families A–F. Alleles excluded by recombination events are marked in pink. The physical locations of the polymorphic microsatellites are given near the haplotype for individual AI-2.

      Case: Family C Proband CII-2, male, Arabic, Israeli, 32yo at report

      CasePresentingHPOs: HP:0000953, HP:0030053, HP:0000998, HP:0008064, HP:0001433, HP:0001634, HP:0001935, HP:0033211, HP:0003565, HP:0000027, HP:0100324, HP:0002716, HP:0100727, HP:0001084

      CasePresentingHPOsFreeText: scrotal masses, Testicular ultrasound examination done in patient C2 revealed echogenic thickening of both the spermatic cords and the scrotal sac, normal-sized testes with a few microcalcifications; extreme infiltration of the subcutis in the lower abdominal wall and thighs was noted in patient C2 by computed tomography scan; nonspecific inflammatory infiltrates in the portal spaces on liver biopsy; nonspecific pathological deviations on bone marrow biopsy

      CaseNOTHPOs: HP:0000054, HP:0002619, HP:0000365, HP:0000520, HP:0012385, HP:0007380

      CaseNOTHPOSFreeText: dilated scleral vessels

      CasePreviousTesting: direct sequencing of AIFM2, ADAMTS14, EIF4EBP2, C10ORF54, PPA1, H2AFY2, LRRC20, NODAL, PRF1, TYSND1, SAR1A, PSAP, NPFFR1, and C10ORF27

      CaseGenotypingMethod: microarray, haplotype analysis, direct sequencing of exons of SLC29A3, restriction digestion

      Variant: G437R homozygous

      ClinVarID: or CAID: 565/CA114352

      gnomAD: The missense variant G437R is present in gnomAD v4.0.0 with a MAF=0.00006666 (4/60002 alleles) in the Admixed American population and 0 homozygotes.

      AddCaseInfo: consanguineous, heterozygous parents. brother (CII-4) is also genotype/phenotype +

      PreviouslyPublished: PMID: 18410979

      VariantEvidence: Kang et al. (2010; PMID: 20595384) performed functional characterization of the G437R mutation in Xenopus oocytes and observed transport activity that was approximately half that of wildtype SLC29A3. Studies in NIH 3T3 fibroblasts demonstrated accelerated turnover of the G437R mutant compared to wildtype, suggesting decreased stability.

      CaseInfo Individual PreviouslyPublished ClinVarID: 565 CA114352 inferred_gene_hgnc:23096 inferred_gene_source:CAID UNC Biocuration Core
    5. ClingenBaseline 23 Oct 2026
      Figure 2Haplotype Analysis Performed in Six Families with H SyndromeAffected individuals are marked by gray symbols. The disease-associated haplotypes in the linked interval on chromosome 10q21.3–q22.1 are shown by vertical bars (red and green) in families A–F. Alleles excluded by recombination events are marked in pink. The physical locations of the polymorphic microsatellites are given near the haplotype for individual AI-2.

      Case: Family D Proband DII-2, male, Arabic, Israeli, 33yo at report

      CasePresentingHPOs: HP:0000953, HP:0030053, HP:0000998, HP:0008064, HP:0000054, HP:0000771, HP:0001433, HP:0002619, HP:0001684, HP:0001634, HP:0000365, HP:0000520, HP:0007380, HP:0001935, HP:0003565, HP:0008734, HP:0000027, HP:0002716, HP:0100727, HP:0100324

      CasePresentingHPOsFreeText: scrotal masses, thickened scrotal sac, retracted penis, nonspecific inflammatory infiltrates in the portal spaces on liver biopsy

      CaseNOTHPOs: HP:0012385

      CaseNOTHPOSFreeText: Dilated scleral vessels

      CasePreviousTesting: direct sequencing of AIFM2, ADAMTS14, EIF4EBP2, C10ORF54, PPA1, H2AFY2, LRRC20, NODAL, PRF1, TYSND1, SAR1A, PSAP, NPFFR1, and C10ORF27

      CaseGenotypingMethod: microarray, haplotype analysis, direct sequencing of exons of SLC29A3, restriction digestion

      Variant: G437R homozygous

      ClinVarID: or CAID: 565/CA114352

      gnomAD: The missense variant G437R is present in gnomAD v4.0.0 with a MAF=0.00006666 (4/60002 alleles) in the Admixed American population and 0 homozygotes.

      AddCaseInfo: consanguineous, heterozygous parents. brothers (DII-5 and DII-7) are also genotype/phenotype +. brothers (DII-8, DII-9, and DII-11) are het and unaffected. brother DII-10 was affected but deceased so no genotype recorded

      PreviouslyPublished: PMID: 18410979

      VariantEvidence: Kang et al. (2010; PMID: 20595384) performed functional characterization of the G437R mutation in Xenopus oocytes and observed transport activity that was approximately half that of wildtype SLC29A3. Studies in NIH 3T3 fibroblasts demonstrated accelerated turnover of the G437R mutant compared to wildtype, suggesting decreased stability.

      CaseInfo Individual PreviouslyPublished ClinVarID: 565 CA114352 inferred_gene_hgnc:23096 inferred_gene_source:CAID UNC Biocuration Core
    6. ClingenBaseline 22 Oct 2026
      Figure 2Haplotype Analysis Performed in Six Families with H SyndromeAffected individuals are marked by gray symbols. The disease-associated haplotypes in the linked interval on chromosome 10q21.3–q22.1 are shown by vertical bars (red and green) in families A–F. Alleles excluded by recombination events are marked in pink. The physical locations of the polymorphic microsatellites are given near the haplotype for individual AI-2.

      Case: Family F Proband FII-6, female, Arabic, Israeli, 27yo at report

      CasePresentingHPOs: HP:0000953, HP:0030053, HP:0000998, HP:0002619, HP:0000520, HP:0007380, HP:0100324, HP:0100727

      CasePresentingHPOsFreeText: dilated scleral vessels

      CaseNOTHPOs: HP:0008064, HP:0001433, HP:0011025, HP:0000365, HP:0012385

      CaseNOTHPOSFreeText:

      CasePreviousTesting: direct sequencing of AIFM2, ADAMTS14, EIF4EBP2, C10ORF54, PPA1, H2AFY2, LRRC20, NODAL, PRF1, TYSND1, SAR1A, PSAP, NPFFR1, and C10ORF27

      CaseGenotypingMethod: microarray, haplotype analysis, direct sequencing of exons of SLC29A3, restriction digestion

      Variant: G437R homozygous

      ClinVarID: or CAID: 565/CA114352

      gnomAD: The missense variant G437R is present in gnomAD v4.0.0 with a MAF=0.00006666 (4/60002 alleles) in the Admixed American population and 0 homozygotes.

      AddCaseInfo: consanguineous parents, not genotyped. brother (FII-5) is het and unaffected.

      PreviouslyPublished: PMID: 18410979

      VariantEvidence: Kang et al. (2010; PMID: 20595384) performed functional characterization of the G437R mutation in Xenopus oocytes and observed transport activity that was approximately half that of wildtype SLC29A3. Studies in NIH 3T3 fibroblasts demonstrated accelerated turnover of the G437R mutant compared to wildtype, suggesting decreased stability.

      CaseInfo Individual PreviouslyPublished ClinVarID: 565 CA114352 inferred_gene_hgnc:23096 inferred_gene_source:CAID UNC Biocuration Core
    7. ClingenBaseline 21 Oct 2026
      Figure 2Haplotype Analysis Performed in Six Families with H SyndromeAffected individuals are marked by gray symbols. The disease-associated haplotypes in the linked interval on chromosome 10q21.3–q22.1 are shown by vertical bars (red and green) in families A–F. Alleles excluded by recombination events are marked in pink. The physical locations of the polymorphic microsatellites are given near the haplotype for individual AI-2.

      Case: Family E Proband EII-1, male, Arabic, Israeli, 17yo at report

      CasePresentingHPOs: HP:0000953, HP:0030053, HP:0000998, HP:0000054, HP:0000771, HP:0002619, HP:0001433, HP:0000520, HP:0012385, HP:0003565

      CasePresentingHPOsFreeText: scrotal masses, dilated scleral vessels, maturation arrest in all tubules with few spermatids in 4% to 5% of the tubules on testicular biopsy

      CaseNOTHPOs: HP:0008064, HP:0011025, HP:0000365, HP:0007380

      CaseNOTHPOSFreeText:

      CasePreviousTesting: direct sequencing of AIFM2, ADAMTS14, EIF4EBP2, C10ORF54, PPA1, H2AFY2, LRRC20, NODAL, PRF1, TYSND1, SAR1A, PSAP, NPFFR1, and C10ORF27

      CaseGenotypingMethod: microarray, haplotype analysis, direct sequencing of exons of SLC29A3, restriction digestion

      Variant: G437R homozygous

      ClinVarID: or CAID: 565/CA114352

      gnomAD: The missense variant G437R is present in gnomAD v4.0.0 with a MAF=0.00006666 (4/60002 alleles) in the Admixed American population and 0 homozygotes.

      AddCaseInfo: consanguineous, heterozygous, unaffected parents.

      PreviouslyPublished: PMID: 18410979

      VariantEvidence: Kang et al. (2010; PMID: 20595384) performed functional characterization of the G437R mutation in Xenopus oocytes and observed transport activity that was approximately half that of wildtype SLC29A3. Studies in NIH 3T3 fibroblasts demonstrated accelerated turnover of the G437R mutant compared to wildtype, suggesting decreased stability.

      CaseInfo Individual PreviouslyPublished ClinVarID: 565 CA114352 inferred_gene_hgnc:23096 inferred_gene_source:CAID UNC Biocuration Core
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    ncbi.nlm.nih.gov/pmc/articles/PMC2561939/
  3. academic.oup.com academic.oup.com
    SLC29A3 gene is mutated in pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome and interacts with the insulin signaling pathway
    1
    1. ClingenBaseline 24 Oct 2026
      RESULTS Gene and mutation identification Analysis of the single nucleotide polymorphism (SNP) microarray genotypes from six patients with PHID identified a single common 1.4 Mb region of shared homozygosity within cytogenetic band 10q22.1, between SNPs rs10509321 and rs1900515 (Fig. 1A). Inspection of the Ensembl and UCSC Genome Browsers demonstrated that the region included 14 known and predicted genes: ADAMTS14, C10orf27, CDH23, EIF4EBP2, LRRC2, KIAA1274, NODAL, NPFFR1, PCBD1, PPA1, PRF1, SLC29A3, SGPL1, UNC5B. Positional candidate genes were selected for sequencing in order to identify pathogenic mutations (Fig. 1B). Five different homozygous mutations were identified in the SLC29A3 gene encoding the equilibrative nucleoside transporter 3 (Fig. 1C, Table 1). Human ENT3 has been shown recently to be the cause of H syndrome, an autosomal recessive disorder with overlapping skin features to PHID (6), indicating that these are allelic disorders. hENT3 belongs to a structurally unique protein family of nucleoside and/or nucleobase transporters (13,14). The five homozygous mutations identified segregated with the disease within each family and were not present in over 100 Lebanese and Pakistani control chromosomes. Figure 1.Open in new tabDownload slideHomozygosity mapping and mutation results in five PHID families. (A) Homozygosity mapping of chromosome 10. Red bars indicate heterozygous single nucleotide polymorphisms (SNPs); blue bars, an extended run of homozygous SNPs greater than would be predicted by chance; green bars, a run of homozygous SNPs but insufficient to meet criteria for significance. (B) Genes within the 1.4 Mb interval bounded by heterozygous SNPs rs10509321 (CII.3) and rs1900515 (DII.1). (C) SLC29A3 sequence electrophoretograms demonstrating homozygous mutations in five PHID families. (D) Protein structure prediction of hENT3 by SVMTM software. (E) Multispecies alignment of the second transmembrane and the C-terminal cytoplasmic domains of ENT3 protein (accession numbers: Homo sapiens, NP_060814.4; Canis lupus, XP_546152.2; Bos taurus, XP_580640.3; Mus musculus, NP_076085.1; monodelphus domesticus, XP_001344438.1; Gallus gallus, XP_421594.2; Gasterosteus aculeatus, ENSGACP00000006741; Takifugu rubipens, ENSTRUP00000028258; Drosophila melangaster, FBpp0077753; Caenorhabditis elegans, NP_501807.3). Table 1.Mutation summary Mutation NM_018344.4 . Protein CCDS7310.1 . Protein domain . Predicted . Mutation predictions . Grantham . SIFT . c.347T>Gp.Met116ArgTransmembrane Domain 2Missense Hydrophobic to large basic910.03c.940delTp.Tyr314ThrfsX91Transmembrane Domain 7Frameshift––c.1309G>Ap.Gly437ArgIntra-cytoplasmic DomainMissense Small hydrophobic to large basic12512.0c.1330G>Tp.Glu444XIntra-cytoplasmic DomainNonsense––c.1346C>Gp.Thr449ArgIntra-cytoplasmic DomainMissense Small polar to large basic710.03Mutation NM_018344.4 . Protein CCDS7310.1 . Protein domain . Predicted . Mutation predictions . Grantham . SIFT . c.347T>Gp.Met116ArgTransmembrane Domain 2Missense Hydrophobic to large basic910.03c.940delTp.Tyr314ThrfsX91Transmembrane Domain 7Frameshift––c.1309G>Ap.Gly437ArgIntra-cytoplasmic DomainMissense Small hydrophobic to large basic12512.0c.1330G>Tp.Glu444XIntra-cytoplasmic DomainNonsense––c.1346C>Gp.Thr449ArgIntra-cytoplasmic DomainMissense Small polar to large basic710.03 Open in new tab Table 1.Mutation summary Mutation NM_018344.4 . Protein CCDS7310.1 . Protein domain . Predicted . Mutation predictions . Grantham . SIFT . c.347T>Gp.Met116ArgTransmembrane Domain 2Missense Hydrophobic to large basic910.03c.940delTp.Tyr314ThrfsX91Transmembrane Domain 7Frameshift––c.1309G>Ap.Gly437ArgIntra-cytoplasmic DomainMissense Small hydrophobic to large basic12512.0c.1330G>Tp.Glu444XIntra-cytoplasmic DomainNonsense––c.1346C>Gp.Thr449ArgIntra-cytoplasmic DomainMissense Small polar to large basic710.03Mutation NM_018344.4 . Protein CCDS7310.1 . Protein domain . Predicted . Mutation predictions . Grantham . SIFT . c.347T>Gp.Met116ArgTransmembrane Domain 2Missense Hydrophobic to large basic910.03c.940delTp.Tyr314ThrfsX91Transmembrane Domain 7Frameshift––c.1309G>Ap.Gly437ArgIntra-cytoplasmic DomainMissense Small hydrophobic to large basic12512.0c.1330G>Tp.Glu444XIntra-cytoplasmic DomainNonsense––c.1346C>Gp.Thr449ArgIntra-cytoplasmic DomainMissense Small polar to large basic710.03 Open in new tab Two novel homozygous mutations predicted to cause premature protein truncation were identified, a 1 bp deletion c.940delT and a nonsense mutation c.1330G>T. The deletion causes a frame shift mutation p.Y314Tfs in transmembrane domain 7 and is predicted to result in the substitution of transmembrane domains 8–11 with an irrelevant protein sequence of 91 amino acids derived from an alternate reading frame. The nonsense mutation p.E444X is predicted to lead to premature protein truncation with loss of part of the final cytoplasmic domain and transmembrane domain 11 of hENT3. It would appear unlikely that the either residual protein would be capable of nucleoside transport function.Three homozygous missense mutations of SLC29A3 were identified to involve conserved amino acids (Table 1). The first missense mutation involves Methionine116 in transmembrane domain 2, which is a hydrophobic amino acid in species as distantly related as humans and nematodes, with a large basic amino acid, Arginine (p.M116R; Fig. 1C and E). The Grantham score for this substitution is 91, which is classified as a moderate change (15). Analysis using the SIFT prediction software also classifies this as a likely deleterious change (16). The introduction of a large basic amino acid into a transmembrane domain would likely result in significant disruption of the hydrophobic nature of the domain and result in retention of the transporter protein within the endoplasmic reticulum, as has been demonstrated for other membrane proteins (17).The second missense change is a recently reported Glycine to Arginine substitution at hENT3 amino acid 437 (p.G437R Fig. 1C), which is located in the putative cytoplasmic domain between transmembrane domains 10 and 11. This is the only mutation in the PHID cohort that is shared with the known mutations in H syndrome. Of particular interest is the observation that this is the sole individual in the PHID cohort who has not developed insulin-dependent DM. The p.G437R change involves the substitution of a large basic amino acid at a position where 41 members of the ENT family as distantly related as humans and Arabidopsis thaliana encode a small hydrophobic amino acid (Fig. 1E) (18). The Grantham difference for this change is 125 and is classified as a moderately radical change.The third missense change occurs at hENT3 amino acid residue 449, which is also located in the final putative intracellular domain between transmembrane domains 10 and 11, and involves the substitution of a Threonine by an Arginine (p.T449R). The amino acids encoded at this position in hENT3 orthologs are small polar/uncharged or small hydrophobic residues (Fig. 1E). Substitution by arginine is associated with a Grantham score of 71 and is predicted by SIFT as not to be tolerated.

      Case: Family C/Prendiville Patient 2, Lebanese-Australian, 11yo at report

      Not scoring this proband since this variant has been reported many times already and parents are consanguineous, from Lebanon which is near many of the other cases

      CaseInfo Individual CA114352 ClinVarID: 565 inferred_gene_hgnc:23096 inferred_gene_source:CAID UNC Biocuration Core
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    academic.oup.com/hmg/article/18/12/2257/645278
  4. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Mutations in SLC29A3, Encoding an Equilibrative Nucleoside Transporter ENT3, Cause a Familial Histiocytosis Syndrome (Faisalabad Histiocytosis) and Familial Rosai-Dorfman Disease
    1
    1. ClingenBaseline 23 Oct 2026
      Familial SHML

      Case: Family 2 Kismet Proband, Turkish, male

      CasePresentingHPOs: HP:0000407, HP:0002240, HP:0004322, HP:0025289, HP:0033176, HP:0100727

      CasePresentingHPOsFreeText: Rapidly growing orbital mass with SHML histopathology. Retropharyngeal lymphadenopathy. Filling of lymph node sinuses with histiocytes, plasma cells and lymphocytes. Histiocytes had a benign appearance, were CD-1a negative but positive for CD68 and S-100.

      CaseNOTHPOs:

      CaseNOTHPOSFreeText:

      CasePreviousTesting: direct sequencing of PRF1 and UNC5B

      CaseGenotypingMethod: genotyping (genome-wide linkage scan was performed using Affymetrix 250k SNP arrays), direct sequencing, PCR

      Variant: p.Gly437Arg; p.Phe103X

      ClinVarID: or CAID: 565; 30947

      gnomAD: The missense variant G437R is present in gnomAD v4.0.0 with a MAF=0.00006666 (4/60002 alleles) in the Admixed American population and 0 homozygotes.

      The nonsense variant, p.Phe103Ter found in exon 2/6, is present in gnomAD v4.0.0 with a MAF=0.0005201 (3/5768 alleles) in the Middle Eastern population and 0 homozygotes.

      AddCaseInfo: 2 affected brothers

      PreviouslyPublished: 16118898

      VariantEvidence: Functional characterization of G437R in Xenopus oocytes showed that transport activity was approximately half of WT SLC29A3. Studies in NIH 3T3 fibroblasts demonstrated accelerated turnover of the G437R mutant compared to WT, suggesting decreased stability (Kang et al. 2010; PMID: 20595384)

      CaseInfo Individual ClinVarID: 30947 CA129560 ClinVarID: 565 CA114352 inferred_gene_hgnc:23096 inferred_gene_source:CAID UNC Biocuration Core
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    ncbi.nlm.nih.gov/pmc/articles/PMC2816679/