Submissions for variant NM_000277.3(PAH):c.168G>A (p.Glu56=)

dbSNP: rs199475567

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen PAH Variant Curation Expert Panel	RCV001093508	SCV001250532	uncertain significance	Phenylketonuria	2019-11-10	reviewed by expert panel	curation	The c.168G>A (p.Glu56=) variant in PAH has been reported as a polymoprhism. It was found in Arab patients' DNA, including patients and controls (zygosity not reported). (BS2; PMID: 18299955) However, this variant is absent from 1000G, ESP, ExAC and gnomAD (PM2). While it is a synonymous variant, alteration of the WT donor site affecting splicing is suggested by Human Splicing Finder and Alamut (PP3). It was observed in cis with a pathogenic variant, IVS2+1G>A (BP2; PMID: 24368688). In summary, this variant meets criteria to be classified as uncertain significance for PAH due to conflicting evidence. ACMG/AMP criteria applied: BS2, BP2, PM2, PP3.
PreventionGenetics, part of Exact Sciences	RCV000249357	SCV000303445	likely benign	not specified		criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV001093508	SCV002777007	uncertain significance	Phenylketonuria	2022-01-14	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000088851	SCV005191951	uncertain significance	not provided		criteria provided, single submitter	not provided
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	RCV000088851	SCV000119446	not provided	not provided		no assertion provided	not provided