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]

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Variant: NM_000277.2(PAH):c.793T>G (p.Cys265Gly)

CA229762

102835 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 44e8290e-d631-475f-9b2e-aa8bdf388e8d

HGVS expressions

NM_000277.2:c.793T>G

NM_000277.2(PAH):c.793T>G (p.Cys265Gly)

NC_000012.12:g.102852864A>C

CM000674.2:g.102852864A>C

NC_000012.11:g.103246642A>C

CM000674.1:g.103246642A>C

NC_000012.10:g.101770772A>C

NG_008690.1:g.69739T>G

NG_008690.2:g.110547T>G

ENST00000553106.6:c.793T>G

ENST00000307000.7:c.778T>G

ENST00000549247.6:n.552T>G

ENST00000553106.5:c.793T>G

NM_000277.1:c.793T>G

NM_001354304.1:c.793T>G

NM_000277.3:c.793T>G

NM_001354304.2:c.793T>G

NM_000277.3(PAH):c.793T>G (p.Cys265Gly)

Uncertain Significance

PP3 PM2

PM5

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.793T>G (p.Cys265Gly) variant in PAH has not been reported in the literature to our knowledge. Reference in BioPKU/PAHdb does not include a case report for this variant (PMID:9781015). This variant is absent from ExAC, gnomAD, 1000G, and ESP. Multiple lines of computational evidence support a deleterious effect (REVEL=0.822). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP3.

PP3

Damaging in SIFT, MutationTaster, benign in Polyphen2. REVEL=0.822 (>0.75)

PM2

Absent from ExAC, gnomAD, 1000G, ESP

PM5

C265Y, LP; C265R, VUS

Approved on: 2022-03-13

Published on: 2022-04-16

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