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

CA16020719

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 9ffeebb5-c4e1-48c9-8640-d8d6b0df1676

HGVS expressions

NM_000277.1:c.47C>A

NC_000012.12:g.102917084G>T

CM000674.2:g.102917084G>T

NC_000012.11:g.103310862G>T

CM000674.1:g.103310862G>T

NC_000012.10:g.101834992G>T

NG_008690.1:g.5519C>A

NG_008690.2:g.46327C>A

NM_000277.2:c.47C>A

NM_001354304.1:c.47C>A

NM_000277.3:c.47C>A

ENST00000307000.7:c.-101C>A

ENST00000546844.1:c.47C>A

ENST00000547319.1:n.358C>A

ENST00000549111.5:n.143C>A

ENST00000550978.6:n.31C>A

ENST00000551337.5:c.47C>A

ENST00000551988.5:n.136C>A

ENST00000553106.5:c.47C>A

ENST00000635500.1:n.29-4186C>A

Uncertain Significance

PP4 PM2

PP3 BP4

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

VUS: The c.47C>A (p.S16Y) variant in PAH was reported in one patient in a PKU cohort without segregation, and evidence of BH4 responsiveness (PP4, PMID: 21307867). This variant is absent from population databases, including 1000 Genomes, gnomAD and ESP. Computations predictors SIFT and Polyphen are conflicting, REVEL=0.569. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PP4, PM2.

PP4

The variant was found in one chromosome of a Japanese patient with PKU. Patient's genotype was not provided, and not determined if BH4 responsive. PMID: 21307867

This study sequenced 203 Japanese patients with PKU. The variant was found in one chromosome. Patient's genotype was not provided, and not determined if BH4 responsive. PubMed:21307867

PM2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP3

SIFT and Polyphen conflicting.

BP4

SIFT and Polyphen conflicting.

Approved on: 2019-02-26

Published on: 2019-04-06

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