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.1237C>T (p.Arg413Cys)

CA229412

102576 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 3ce7ed5e-f479-48ba-b20f-b2efc8d8466f

HGVS expressions

NM_000277.3:c.1237C>T

NM_000277.3(PAH):c.1237C>T (p.Arg413Cys)

NC_000012.12:g.102840478G>A

CM000674.2:g.102840478G>A

NC_000012.11:g.103234256G>A

CM000674.1:g.103234256G>A

NC_000012.10:g.101758386G>A

NG_008690.1:g.82125C>T

NG_008690.2:g.122933C>T

NM_000277.1:c.1237C>T

NM_000277.2:c.1237C>T

NM_001354304.1:c.1237C>T

NM_001354304.2:c.1237C>T

ENST00000307000.7:c.1222C>T

ENST00000551114.2:n.899C>T

ENST00000553106.5:c.1237C>T

ENST00000635477.1:n.341C>T

ENST00000635528.1:n.752C>T

Uncertain Significance

PP3 PM2 PM5

PP4

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The variant c.1237C>T (p.Arg313Cys) in PAH is not currently reported in patients in the literature. This variant is predicted deleterious by SIFT, PolyPhen2, MutationTaster, and REVEL = 0.937 (PP3), and has an extremely low frequency in gnomAD (PM2). This variant is at the same codon as c.1238G>C (p.Arg413Pro) which has been curated as pathogenic by the ClinGen PAH VCEP (ClinVarID:592) (PM5). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM5, PP3.

PP3

Predicted deleterious by SIFT, PolyPhen2, MutationTaster, and REVEL = 0.937.

PM2

Extremely low frequency in gnomAD (MAF = 0.00007, South Asain population)

PM5

c.1238G>C (p.Arg413Pro) has been curated as pathogenic by the ClinGen PAH VCEP (ClinVarID:592); c.1237C>A (p.Arg413Ser) - ClinVarID: 102757, no assertion, has not yet been curated by ClinGen PAH VCEP; c.1237C>G (p.Arg413Gly) not reported in ClinVar and has not yet been curated by ClinGen PAH VCEP

PP4

R413C not currently reported in patients in the literature

Approved on: 2020-05-14

Published on: 2020-05-14

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