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]

Link to SEPIO compliant JSON-LD document

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

CA242485549

725756 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

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

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

Approved on: 2023-07-23

Published on: 2023-07-23

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