Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000277.3(PAH):c.456T>C (p.Pro152=)

CA242485549

725756 (ClinVar)

Gene: PAH (HGNC:5053)

Condition: phenylketonuria (MONDO:0009861)

Inheritance Mode: Autosomal recessive inheritance

UUID: 9d7fc507-0f5a-4c53-8562-ff01cc576656

Approved on: 2023-07-23

Published on: 2023-07-23

HGVS expressions

NM_000277.3:c.456T>C

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

NC_000012.12:g.102866649A>G

CM000674.2:g.102866649A>G

NC_000012.11:g.103260427A>G

CM000674.1:g.103260427A>G

NC_000012.10:g.101784557A>G

NG_008690.1:g.55954T>C

NG_008690.2:g.96762T>C

ENST00000553106.6:c.456T>C

ENST00000307000.7:c.441T>C

ENST00000549111.5:n.552T>C

ENST00000551988.5:n.530+10813T>C

ENST00000553106.5:c.456T>C

NM_000277.1:c.456T>C

NM_000277.2:c.456T>C

NM_001354304.1:c.456T>C

NM_001354304.2:c.456T>C

Uncertain Significance

PM2_Supporting

BP7

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

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.

PM2_Supporting

This variant is absent in gnomAD v2.1.1 (PM2_Supporting).

BP7

Silent variant not predicted to alter splicing by SpliceAI (all scores <0.2) but nucleotide is conserved from human through chicken

Curation History

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. If you have questions about the information contained on this website, please see a health care professional.