ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.47_48dup (p.Asp17fs)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel RCV003479538 SCV004222630 pathogenic Phenylketonuria 2023-10-15 reviewed by expert panel curation The c.47_48dup (p.Asp17LeufsTer22) variant in PAH is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 1/13 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant is reported on 3 alleles of patients with phenylketonuria, with BH4 deficiency excluded (PP4_moderate, PMID: 21147011). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal recessive PAH deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen PAH VCEP: PVS1, PP4_moderate, PM2_supporting. (Phenylketonuria VCEP specifications version 1).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.