Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001269073 | SCV001448297 | pathogenic | Phenylketonuria | 2020-10-15 | reviewed by expert panel | curation | This c.707-1G>C (aka IVS6-1G>C) variant in PAH has been observed in one patient with classic PKU, in trans with pathogenic variant c.441+5G>T (PMID: 30159852). This variant is absent from controls in population databases. This variant in the -1 splice acceptor site of intron 6 results in exon skipping or use of a cryptic splice site. The variant disrupts the reading frame and is predicted to undergo nonsense mediated decay. This variant breaks the splice site in intron 6 according to computational models. In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PM3, and PP4. |