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:c.134T>C

CA16020730

Gene: PAH (HGNC:5053)

Condition: phenylketonuria (MONDO:0009861)

Inheritance Mode: Autosomal recessive inheritance

UUID: b21b61c5-295c-4c84-9398-395bfe6b5da3

Approved on: 2019-04-04

Published on: 2019-08-16

HGVS expressions

NM_000277.3:c.134T>C

NC_000012.12:g.102912825A>G

CM000674.2:g.102912825A>G

NC_000012.11:g.103306603A>G

CM000674.1:g.103306603A>G

NC_000012.10:g.101830733A>G

NG_008690.1:g.9778T>C

NG_008690.2:g.50586T>C

NM_000277.1:c.134T>C

NM_000277.2:c.134T>C

NM_001354304.1:c.134T>C

ENST00000307000.7:c.119T>C

ENST00000546844.1:c.134T>C

ENST00000548677.2:n.221T>C

ENST00000548928.1:n.56T>C

ENST00000549111.5:n.230T>C

ENST00000550978.6:n.118T>C

ENST00000551337.5:c.134T>C

ENST00000551988.5:n.223T>C

ENST00000553106.5:c.134T>C

ENST00000635500.1:n.102T>C

Uncertain Significance

PP4 PM2

PP3 PM3

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.134T>C (p.Val45Ala) PAH variant has been reported in a patient with mild hyperphenylalaninemia (PMID: 22513348). This variant is absent from 1000G, ESP, and gnomAD databases. It is a missense variant with conflicting predictions of pathogenicity: SIFT: Tolerated, PolyPhen: Benign, MutationTaster: Disease causing, REVEL=0.697. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP4.

PP4

Detected in a patient with MHP, BH4 deficiency not reported to be ruled out PMID: 22513348

p.V45A was detected in a patient with MHP (Phe < 0.6 mmol/L on a normal diet). PubMed:22513348

PM2

Absent from ExAC, gnomAD, 1000G, ESP.

PP3

Conflicting predictions of pathogenicity: SIFT: Tolerated, PolyPhen: Benign, MutationTaster: Disease causing; REVEL=0.697.

PM3

detected with p.P281L, but segregation studies not reported

Patient 62 genotype: p.V45A p.P281L, but no segregation studies reported PubMed:22513348

Curation History

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