Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
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. |
De |
RCV000088903 | SCV000119501 | not provided | not provided | no assertion provided | not provided |