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

CA16020925

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: d3a1e839-a01d-4fbb-8e6f-e17329ab880e

HGVS expressions

NM_001354304.2:c.1066-13T>G

NC_000012.12:g.102843792A>C

CM000674.2:g.102843792A>C

NC_000012.11:g.103237570A>C

CM000674.1:g.103237570A>C

NC_000012.10:g.101761700A>C

NG_008690.1:g.78811T>G

NG_008690.2:g.119619T>G

NM_000277.1:c.1066-13T>G

NM_000277.2:c.1066-13T>G

NM_001354304.1:c.1066-13T>G

NM_000277.3:c.1066-13T>G

ENST00000307000.7:c.1051-13T>G

ENST00000549247.6:n.825-13T>G

ENST00000551114.2:n.728-13T>G

ENST00000553106.5:c.1066-13T>G

ENST00000635477.1:n.170-13T>G

ENST00000635528.1:n.581-13T>G

Uncertain Significance

PP4 PM3 PM2

PP3

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

(PAH):c.1066-13T>G is an intronic variant with conflicting in silico evidence in splicing impact. This variant was documented in a patient with moderate PKU in trans with pathogenic variant p.R243Q (PMID 24705691). This variant is absent from population databases. In summary, this variant has insufficient evidence and is classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM3, and PP4.

PP4

This variant was documented in a patient in a Chinese cohort with moderate PKU and the patient was compound heterozygous for the variant (PMID 24705691).

PM3

This variant was documented in a patient in a Chinese cohort with moderate PKU in trans with pathogenic variant p.R243Q. Parental analysis was performed to confirm compound heterozygosity. (PMID 24705691).

PM2

This variant is absent from population databases GnomAD and ExAC.

PP3

Conflicting in silico evidence in splicing impact. Splicing AI predicts a low probability of a splice-altering event (0.28) and TraP score predicts a deleterious impact (0.485) greater than the 99th percentile.

Approved on: 2020-07-25

Published on: 2020-07-25

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