ClinVar Miner

Submissions for variant NM_000380.3(XPA):c.323G>A (p.Cys108Tyr) (rs104894131)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Miraca Genetics Laboratories, RCV000672811 SCV000807586 uncertain significance Xeroderma pigmentosum, type 1 2017-09-01 criteria provided, single submitter clinical testing This variant was found once in our laboratory homozygous in a 9-year-old male with photosensitivity and learning problems. A similarly affected sister, who also had ataxia, was also homozygous.
Counsyl RCV000672811 SCV000797955 uncertain significance Xeroderma pigmentosum, type 1 2018-02-22 criteria provided, single submitter clinical testing
GeneDx RCV000492893 SCV000583159 likely pathogenic not provided 2015-08-18 criteria provided, single submitter clinical testing The C108Y variant in the XPA gene has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The C108Y variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The C108Y variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense pathogenic variants in the same residue (C108F) has been reported in the Human Gene Mutation Database in association with xeroderma pigmentosum (Stenson et al., 2014), supporting the functional importance of this region of the protein. The C108Y variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded

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