Submissions for variant NM_000277.3(PAH):c.462C>A (p.Tyr154Ter)

dbSNP: rs1191473722

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen PAH Variant Curation Expert Panel	RCV001269276	SCV001448612	pathogenic	Phenylketonuria	2020-10-15	reviewed by expert panel	curation	This variant c.462C>A (p.Tyr154Ter) in PAH was reported in at least 1 Han Chinese patient with PAH deficiency (paper did not specify how many patients had this variant) (PMID: 28982351), although a defect in BH4 metabolism was excluded by urinary pterin analysis only. This is a nonsense variant in exon 5 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. This variant is absent in population databases. In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PP4.
Baylor Genetics	RCV001269276	SCV004209638	likely pathogenic	Phenylketonuria	2023-07-14	criteria provided, single submitter	clinical testing
Neonatal Disease Screening Center, Medical Genetics Center, Huaihua City Maternal and Child Health Care Hospital	RCV001269276	SCV004800895	pathogenic	Phenylketonuria		no assertion criteria provided	clinical testing	PVS1+PM2+PM3_S+PP4