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

CA16020754

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 499ada66-0170-422a-a606-9b1958ec54b0

HGVS expressions

NM_000277.3:c.232G>C

NC_000012.12:g.102894855C>G

CM000674.2:g.102894855C>G

NC_000012.11:g.103288633C>G

CM000674.1:g.103288633C>G

NC_000012.10:g.101812763C>G

NG_008690.1:g.27748G>C

NG_008690.2:g.68556G>C

NM_000277.1:c.232G>C

NM_000277.2:c.232G>C

NM_001354304.1:c.232G>C

ENST00000307000.7:c.217G>C

ENST00000546844.1:c.232G>C

ENST00000548677.2:n.319G>C

ENST00000548928.1:n.154G>C

ENST00000549111.5:n.328G>C

ENST00000550978.6:n.216G>C

ENST00000551337.5:c.232G>C

ENST00000551988.5:n.321G>C

ENST00000553106.5:c.232G>C

Uncertain Significance

PP3 PM2 PP4_Moderate

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.232G>C (p.Glu78Gln) variant in PAH has been reported in a patient with PAH deficiecy (BH4 deficiency excluded) (PP4_Moderate; PMID: 26503515) This variant is absent from 1000G, ESP, ExAC and gnomAD (PM2). A deleterious effect is predicted in SIFT, Polyphen-2, MutationTaster. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PP3.

PP3

Predicted deleterious in SIFT (D), Polyphen (P), and MutationTaster (D)

PM2

Absent from controls in ExAC, gnomAD, 1000 Genomes, ESP

PP4_Moderate

Detected on 1 allele. BH4 deficiency ruled out (PMID: 26503515)

PubMed:26503515

Approved on: 2019-11-10

Published on: 2019-11-10

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