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_001354304.2:c.1204T>A

CA16020968

Gene: PAH (HGNC:5053)

Condition: phenylketonuria (MONDO:0009861)

Inheritance Mode: Autosomal recessive inheritance

UUID: 8afe5778-b49b-4919-813c-e0af719d3ac3

Approved on: 2021-05-15

Published on: 2021-09-19

HGVS expressions

NM_001354304.2:c.1204T>A

ENST00000553106.6:c.1204T>A

ENST00000307000.7:c.1189T>A

ENST00000551114.2:n.866T>A

ENST00000553106.5:c.1204T>A

ENST00000635477.1:n.308T>A

ENST00000635528.1:n.719T>A

NM_000277.1:c.1204T>A

NM_000277.2:c.1204T>A

NM_001354304.1:c.1204T>A

NM_000277.3:c.1204T>A

NC_000012.12:g.102840511A>T

CM000674.2:g.102840511A>T

NC_000012.11:g.103234289A>T

CM000674.1:g.103234289A>T

NC_000012.10:g.101758419A>T

NG_008690.1:g.82092T>A

NG_008690.2:g.122900T>A

Uncertain Significance

PP4_Moderate PP3 PM2

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.1204T>A (p.Phe402Ile) variant in PAH has been detected in 1 Japanese patient with mild HPA, BH4 deficiency excluded (PMID: 21307867). This variant is absent from population databases (PM2), and is predicted deleterious by SIFT, PolyPhen2, MutationTaster, and REVEL = 0.946 (PP3). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP3, PP4_M.

PP4_Moderate

F402I detected in 1 Japanese patient with mild HPA, serum Phe = 180-600umol/l - exact Phe level for patient not specified; included analysis of dihydropteridine reductase activity in red blood cells, biopterin loading test and/or pteridine analysis in urine. PMID: 21307867

PP3

Predicted deleterious by SIFT, PolyPhen2, MutationTaster, and REVEL = 0.946.

PM2

Variant absent from population databases.

PM3

Genotype reported as "F402I/sm" where sm= severe mutation

PM5

At same codon as c.1204T>C (p.F402L), c.1204T>G (p.F402V), and c.1205T>G (p.F402V) - all curated as VUS by ClinGen PAH VCEP.

Curation History

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.