ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.359G>A (p.Trp120Ter)

dbSNP: rs199475586
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel RCV001199994 SCV001370833 pathogenic Phenylketonuria 2020-05-08 reviewed by expert panel curation Variant c.359G>A (p.Trp120Ter) in PAH was found in 1 Moroccan patient with Phe levels >600 umol/L (PMID: 19786003) (PP4). This is a nonsense variant in exon 4 out of 13 coding exons, predicted to undergo nonsense mediated mRNA decay, as it is not located in the 3'-most exon or the 3'-most 50 bp of the penultimate exon. The exon is present in biologically-relevant transcripts (PVS1). Patient was found to be homozygous for p.W125X (PMID:19786003) (PM3). Parental and familial DNA was sequenced. Variant was absent from controls in gnomAD, PAGE, 100 Genomes or ESP (PM2). In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied:PVS1, PM3_supporting, PP4, PM2.
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000088903 SCV000119501 not provided not provided no assertion provided not provided

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