Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001375891 | SCV001572847 | pathogenic | Phenylketonuria | 2020-12-07 | reviewed by expert panel | curation | This c.843-1G>A variant in PAH was reported in trans with pathogenic variants p.S70del and p.Arg243Gln in 2 Han Chinese patients with PAH deficiency (PMID: 28982351). This variant is present in European (non-Finnish) populations at an extremely low frequency in gnomAD (MAF=0.000008827). This variant in the -1 splice acceptor site of intron 7 disrupts the reading frame and is predicted to undergo nonsense mediated decay (NMD). The exon is present in biologically-relevant transcripts. In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM3 strong, PM2, PP4 |