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

CA16020871

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 7b926e89-1446-46c1-a71b-756e59f310ae

HGVS expressions

NM_000277.3:c.842+4A>T

NC_000012.12:g.102852811T>A

CM000674.2:g.102852811T>A

NC_000012.11:g.103246589T>A

CM000674.1:g.103246589T>A

NC_000012.10:g.101770719T>A

NG_008690.1:g.69792A>T

NG_008690.2:g.110600A>T

NM_000277.1:c.842+4A>T

NM_000277.2:c.842+4A>T

NM_001354304.1:c.842+4A>T

ENST00000307000.7:c.827+4A>T

ENST00000549247.6:n.601+4A>T

ENST00000553106.5:c.842+4A>T

ENST00000635477.1:n.3+4A>T

Uncertain Significance

PP3 PP4 PM2

PS1 PM3

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.842+4A>T PAH variant has been reported in PKU patients (PMID: 25863075). This variant is absent from 1000G, ESP, and gnomAD databases. This is an intronic variant in a highly conserved nucleotide, and computational analyses predict that this variant abolishes the donor splice site of intron 7. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PP3, PM2, PP4.

PP3

Variant abolishes the splice donor site of intron 7.

PP4

Detected in a patient with phenylketonuria. Article in Chinese.

Six novel mutations, including c.842+4A>T were detected. PubMed:25863075

PM2

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

PS1

Intronic variant

PM3

Reported below. Article in Chinese.

NA PubMed:25863075

Approved on: 2019-06-09

Published on: 2019-06-09

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