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:c.1154T>C

CA16020951

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 11e1322e-9388-417b-aa8f-2016b206fa5a

HGVS expressions

NM_000277.3:c.1154T>C

NC_000012.12:g.102843691A>G

CM000674.2:g.102843691A>G

NC_000012.11:g.103237469A>G

CM000674.1:g.103237469A>G

NC_000012.10:g.101761599A>G

NG_008690.1:g.78912T>C

NG_008690.2:g.119720T>C

ENST00000553106.6:c.1154T>C

ENST00000307000.7:c.1139T>C

ENST00000549247.6:n.913T>C

ENST00000551114.2:n.816T>C

ENST00000553106.5:c.1154T>C

ENST00000635477.1:c.258T>C

ENST00000635528.1:n.669T>C

NM_000277.1:c.1154T>C

NM_000277.2:c.1154T>C

NM_001354304.1:c.1154T>C

NM_001354304.2:c.1154T>C

Likely Pathogenic

PP3 PM3 PM2 PP4_Moderate

PS3 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.1154T>C (p.Leu385Pro) variant in PAH has been reported in at least 3 Chinese patients with Phe > 120umol/L (BH4 deficiency excluded) (PP4_Moderate; PMIDs:29499199, 23932990). This variant was detected in the homozygous state in two patients (PM3; PMID:23932990). This variant is absent in population databases (PM2). This variant is predicted deleterious by SIFT, PolyPhen, MutationTaster, and REVEL = 0.817 (PP3). In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP4_Moderate, PM3, PP3.

PP3

Variant predicted deleterious by SIFT, PolyPhen, MutationTaster, and REVEL = 0.817.

PM3

PMID: 23932990 2 Patients are reported to be homozygous for Leu385Pro - 1.0 points

PM2

Variant absent from population databases

PP4_Moderate

At least 2 classic PKU patients are reported in PMID: 23932990 with Phe >1200umol/L and BH4 deficiency ruled out via urinary pterin analysis with HPLC and DHPR activity assay.

PS3

PMID: 23932990 - predicted null based on identification in patient with classic PKU in homoallelic state

PM5

c.1155G>C (p.L385L) reported in PAH database, but absent in ClinVar and ClinGen Allele Registry, predicted benign by in silico models

Approved on: 2023-10-13

Published on: 2023-10-13

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.