ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.420G>A (p.Ala140=)

gnomAD frequency: 0.00004  dbSNP: rs200366386
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel RCV001279866 SCV004015320 uncertain significance Phenylketonuria 2023-07-23 reviewed by expert panel curation The NM_000277.3:c.420G>A variant in PAH is a synonymous (silent) variant (p.Ala140=) that is not predicted to impact splicing. To our knowledge, this variant has not been reported in the literature and results of functional studies are unavailable. The highest population minor allele frequency in gnomAD v2.1.1 is 0.0001384 (1/7226 alleles) in the Other population, which is lower than the ClinGen PAH VCEP’s threshold for PM2_Supporting (<0.0002), meeting this criterion (PM2_Supporting). There is a ClinVar entry for this variant (Variation ID: 991623, 1 star review status) with one submitter classifying the variant as a variant of uncertain significance and one submitter classifying the variant as likely benign. In summary, this variant meets the criteria to be classified as a variant of uncertain significance for PAH deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen PAH Variant Curation Expert Panel (Specifications Version 2.0): PM2_Supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV001279866 SCV001702734 likely benign Phenylketonuria 2024-11-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV003294179 SCV003996021 likely benign Inborn genetic diseases 2023-05-05 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Natera, Inc. RCV001279866 SCV001466999 uncertain significance Phenylketonuria 2020-04-17 no assertion criteria provided clinical testing

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.