ClinVar Miner

Submissions for variant NM_000194.3(HPRT1):c.481G>A (p.Ala161Thr)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001051587 SCV001215751 likely pathogenic Partial hypoxanthine-guanine phosphoribosyltransferase deficiency; Lesch-Nyhan syndrome 2020-01-03 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 161 of the HPRT1 protein (p.Ala161Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with HPRT1-related conditions (PMID: 19016344, 25136576). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C55"). This variant disrupts the p.Ala161 amino acid residue in HPRT1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19016344, 15386453, 11018746). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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