ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.161T>C (p.Leu54Ser)

gnomAD frequency: 0.00001  dbSNP: rs199475677
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel RCV000669099 SCV001572856 likely pathogenic Phenylketonuria 2020-07-23 reviewed by expert panel curation The c.161T>C (p.Leu54Ser) variant in PAH is a missense variant that is predicted to be deleterious in multiple lines of computational evidence. This variant was reported in a Spanish patient with mild/moderate PKU. A defect in the synthesis or regeneration pathways of 6R-BH4 was ruled out by analyzing urinary pterin levels and measuring the dihydropteridine reductase activity (PMID: 27121329). This variant was detected in trans with pathogenic variant c.912+1G>A. It was found in extremely low frequency in gnomAD (MAF=0.00006). In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP4 moderate, PM3, and PP3.
Counsyl RCV000669099 SCV000793804 uncertain significance Phenylketonuria 2017-11-14 criteria provided, single submitter clinical testing
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000088843 SCV000119436 not provided not provided no assertion provided not provided

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