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_000277.3(PAH):c.1175T>C (p.Phe392Ser)

CA229369

102544 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 4a89f184-bab9-45d5-b0eb-0ad48c77ec55

HGVS expressions

NM_000277.3:c.1175T>C

NM_000277.3(PAH):c.1175T>C (p.Phe392Ser)

NM_000277.1:c.1175T>C

NM_000277.2:c.1175T>C

NM_001354304.1:c.1175T>C

NM_001354304.2:c.1175T>C

ENST00000307000.7:c.1160T>C

ENST00000549247.6:n.934T>C

ENST00000551114.2:n.837T>C

ENST00000553106.5:c.1175T>C

ENST00000635477.1:n.279T>C

ENST00000635528.1:n.690T>C

NC_000012.12:g.102843670A>G

CM000674.2:g.102843670A>G

NC_000012.11:g.103237448A>G

CM000674.1:g.103237448A>G

NC_000012.10:g.101761578A>G

NG_008690.1:g.78933T>C

NG_008690.2:g.119741T>C

Uncertain Significance

PP3 PM5 PM2

PP4

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1175T>C (p.Phe392Ser) variant in PAH was reported in one non-English article that is not accessible (PMID: 22333022). This variant is absent from population databases (PM2), and is predicted deleterious by SIFT, PolyPhen2, MutationTaster, and REVEL = 0.98 (PP3). This variant is same codon as F392I, reported as pathogenic in ClinVar (VarID:852581; 2 submitters) (PM5). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP3, PM5

PP3

Variant predicted deleterious by SIFT, PolyPhen2, MutationTaster, and REVEL = 0.98.

PM5

At same codon as F392I, reported as pathogenic in ClinVar (VarID:852581; 2 submitters)

PM2

Variant absent from population databases.

PP4

F392S reported in an non-English article that is not accessible (PMID: 22333022).

Approved on: 2020-08-31

Published on: 2020-08-31

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.