ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.470G>C (p.Arg157Thr)

dbSNP: rs199475611
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel RCV000758125 SCV000886603 uncertain significance Phenylketonuria 2021-02-14 reviewed by expert panel curation The c.470G>C (p.Arg157Thr) variant in PAH has not been reported in an affected patient to our knowledge. The reference in BioPKU (Carter KC, 1998) does not include this variant. The p.R157T mutant is listed as having 5% of wt PAH activity in vitro (BioPKU), but this likely corresponds to the p.R157N variant (PMID: 9450897). The p.Arg157Asn variant at the same amino acid is interpreted as pathogenic in ClinVar (VarID 590772). p.Arg157Thr is absent from ExAC, gnomAD, 1000G, and ESP. It is predicted deleterious in SIFT, Polyphen-2, MutationTaster, and REVEL=0.95. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM5, PP3.

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