Submissions for variant NM_000277.3(PAH):c.735G>A (p.Val245=)

gnomAD frequency: 0.19782  dbSNP: rs1042503

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen PAH Variant Curation Expert Panel	RCV000297921	SCV000852118	benign	Phenylketonuria	2018-04-24	reviewed by expert panel	curation	The c.735G>A (p.Val245=) variant in PAH has a MAF of 0.29058 in ExAC (BA1; http://exac.broadinstitute.org) with 6,524 homozygotes (BS2). This is a synonymous variant, predicted tolerated and benign in SIFT, Polyphen. MutationTaster predicted polymorphism with no abrogation of splice sites (BP4). In summary, this variant meets criteria to be classified as benign.
Eurofins Ntd Llc (ga)	RCV000078529	SCV000110385	benign	not specified	2018-02-10	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000078529	SCV000303448	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000297921	SCV000375566	benign	Phenylketonuria	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000089066	SCV000696464	benign	not provided	2016-04-05	criteria provided, single submitter	clinical testing	Variant summary: The variant of interest causes a synonymous change involving a non-conserved nucleotide with 3/5 Alamut algorithms predicting the creation of a splice donor site. However, these in silico predictions have not been confirmed with functional studies. This variant was found in 35308/121456 control chromosomes (6524 homozygotes) at a frequency of 0.2907061, which exceeds the predicted the maximal expected frequency of a pathogenic PAH allele (0.0079057), highly suggesting this variant is benign. In addition, a reputable clinical laboratory classifies the variant as Benign. The variant of interest is cited as a known common polymorphism in the literature. Taken together, this variant was classified as a Benign variant.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000297921	SCV000744095	benign	Phenylketonuria	2014-10-10	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000297921	SCV001593192	benign	Phenylketonuria		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000297921	SCV001721840	benign	Phenylketonuria	2024-02-01	criteria provided, single submitter	clinical testing
Pars Genome Lab	RCV000297921	SCV001750006	benign	Phenylketonuria	2021-07-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000089066	SCV001915754	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 29390883, 32668217)
Fulgent Genetics, Fulgent Genetics	RCV000297921	SCV002807378	benign	Phenylketonuria	2021-07-19	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000089066	SCV005235496	benign	not provided		criteria provided, single submitter	not provided
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	RCV000089066	SCV000119672	not provided	not provided		no assertion provided	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000297921	SCV000733123	benign	Phenylketonuria		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000297921	SCV001453110	benign	Phenylketonuria	2020-09-16	no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000078529	SCV001957070	benign	not specified		no assertion criteria provided	clinical testing