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.1249T>G

CA16020982

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 4c782a9b-194f-4bcf-b836-b7f74d93b474

HGVS expressions

NM_000277.1:c.1249T>G

NC_000012.12:g.102840466A>C

CM000674.2:g.102840466A>C

NC_000012.11:g.103234244A>C

CM000674.1:g.103234244A>C

NC_000012.10:g.101758374A>C

NG_008690.1:g.82137T>G

NG_008690.2:g.122945T>G

ENST00000553106.6:c.1249T>G

ENST00000307000.7:c.1234T>G

ENST00000551114.2:n.911T>G

ENST00000553106.5:c.1249T>G

ENST00000635477.1:n.353T>G

ENST00000635528.1:n.764T>G

NM_000277.2:c.1249T>G

NM_001354304.1:c.1249T>G

NM_000277.3:c.1249T>G

NM_001354304.2:c.1249T>G

Likely Pathogenic

PP4 PP3 PM2 PM5

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1249T>G (p.Tyr417Asp) variant in PAH has been reported in 1 individual with PAH deficiency (PMID: 10693064). This variant is absent in population databases. Computational evidence support a deleterious effect. Another missense variant at the same amino acid (p.Tyr417His) is interpreted as pathogenic. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM5, PP3, PP4.

PP4

Y417D found on 1 allele of a hyperphenylalaninaemia patient. (normal values of blood phenylalanine <180 µmol/l). BH4 deficiency not investigated. PMID: 10693064

151 patients with hyperphenylalaninaemia originally from all of the Italian regions. Y417D was found on 1 allele. PubMed:10693064

PP3

Deleterious effect predicted in SIFT, PolyPhen2, MutationTaster, REVEL=0.991

PM2

Absent from ExAC, gnomAD, 1000G, ESP

PM5

p.Tyr417His interpreted as pathogenic by 1 submitter and PAH VCEP

Approved on: 2020-08-13

Published on: 2021-11-21

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