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_000277.1:c.793T>C

CA16020858

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 82c8fa03-325e-41b3-8842-cd318086a159

HGVS expressions

NM_000277.1:c.793T>C

NC_000012.12:g.102852864A>G

CM000674.2:g.102852864A>G

NC_000012.11:g.103246642A>G

CM000674.1:g.103246642A>G

NC_000012.10:g.101770772A>G

NG_008690.1:g.69739T>C

NG_008690.2:g.110547T>C

ENST00000553106.6:c.793T>C

ENST00000307000.7:c.778T>C

ENST00000549247.6:n.552T>C

ENST00000553106.5:c.793T>C

NM_000277.2:c.793T>C

NM_001354304.1:c.793T>C

NM_000277.3:c.793T>C

NM_001354304.2:c.793T>C

Uncertain Significance

PM2 PP4_Moderate PP3

PM3 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>C (p.Cys265Arg) variant in PAH is reported in at least 1 Chinese patient with PAH deficiency (BH4 deficiency ruled out, PMID: 23932990). It was detected in trans with a variant of unknown significance, p.Arg53His (PMID: 30050108). This variant is absent in population databases. Multiple lines of computational evidence support a deleterious effect. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP3, PP4_moderate.

PM2

Absent from ExAC, gnomAD, 1000G, ESP

PP4_Moderate

p.C265R was seen in 1 Chinese Han patient with PAH deficiency. A defect in the synthesis or recycling of tetrahydrobiopterin was excluded. PMID: 23932990

PP3

Predicted deleterious in SIFT, Polyphen2, MutationTaster. REVEL=0.895

PM3

Detected in trans with R53H (VUS, PMID: 30050108) 0.25 points

PM5

C265Y (LP by Invitae); C265G, clinical significance not provided in ClinVar.

Approved on: 2022-03-13

Published on: 2022-04-16

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