Submissions for variant NM_000277.3(PAH):c.456T>C (p.Pro152=)

dbSNP: rs377244118

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen PAH Variant Curation Expert Panel	RCV000899868	SCV004015314	uncertain significance	Phenylketonuria	2023-07-23	reviewed by expert panel	curation	The NM_000277.3:c.456T>C variant in PAH is a synonymous (silent) variant (p.Pro152=) 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. This variant is absent in gnomAD v2.1.1 (PM2_Supporting). There is a ClinVar entry for this variant (Variation ID: 725756, 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	RCV000899868	SCV001044158	likely benign	Phenylketonuria	2024-11-11	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000899868	SCV001455415	uncertain significance	Phenylketonuria	2020-01-24	no assertion criteria provided	clinical testing