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.786C>T (p.Val262=)

CA242471869

883189 (ClinVar)

Gene: PAH (HGNC:5053)

Condition: phenylketonuria (MONDO:0009861)

Inheritance Mode: Autosomal recessive inheritance

UUID: 251ff915-9b59-4b03-8690-7ae55aea4c86

Approved on: 2023-07-23

Published on: 2023-07-23

HGVS expressions

NM_000277.3:c.786C>T

NM_000277.3(PAH):c.786C>T (p.Val262=)

NC_000012.12:g.102852871G>A

CM000674.2:g.102852871G>A

NC_000012.11:g.103246649G>A

CM000674.1:g.103246649G>A

NC_000012.10:g.101770779G>A

NG_008690.1:g.69732C>T

NG_008690.2:g.110540C>T

ENST00000553106.6:c.786C>T

ENST00000307000.7:c.771C>T

ENST00000549247.6:n.545C>T

ENST00000553106.5:c.786C>T

NM_000277.1:c.786C>T

NM_000277.2:c.786C>T

NM_001354304.1:c.786C>T

NM_001354304.2:c.786C>T

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.786C>T in PAH is a synonymous (silent) variant (p.Val262=) 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: 883189, 1 star review status) with two submitters 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

Absent in gnomad

BP7

synonymous (silent) variant that is (p.Val262=) that is not predicted to impact splicing but nucleotide is conserved from humans through zebrafish

Curation History

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