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_000277.1(PAH):c.1162G>A (p.Val388Met)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA251543

619 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: c18b654a-1bd0-428b-b43f-2711b92f28a1

Approved on: 2018-08-05

Published on: 2019-04-05

HGVS expressions

NM_000277.1:c.1162G>A

NM_000277.1(PAH):c.1162G>A (p.Val388Met)

NC_000012.12:g.102843683C>T

CM000674.2:g.102843683C>T

NC_000012.11:g.103237461C>T

CM000674.1:g.103237461C>T

NC_000012.10:g.101761591C>T

NG_008690.1:g.78920G>A

NG_008690.2:g.119728G>A

NM_000277.2:c.1162G>A

NM_001354304.1:c.1162G>A

NM_000277.3:c.1162G>A

ENST00000307000.7:c.1147G>A

ENST00000549247.6:n.921G>A

ENST00000551114.2:n.824G>A

ENST00000553106.5:c.1162G>A

ENST00000635477.1:n.266G>A

ENST00000635528.1:n.677G>A

Pathogenic

PS3 PP3 PP4 PM2 PM3

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

PAH-specific ACMG/AMP criteria applied: PM2: Extremely low in ExAC and 1000 genomes (PMID:9860305); PS3: PAH activity in COS cell expression system 15% (PMID:9860305); PM3: Compound het with severe mutation (PMID:9860305); PP3: ; PP4: Reported in patient with classic PKU (PMID:9860305). In summary this variant meets criteria to be classified as pathogenic for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (PM2, PS3, PM3, PP3, PP4).

PS3

PAH activity in COS cell expression system 15%

PAH activity in COS cell expression system 15% PubMed:9860305

PP3

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

PP4

Reported in patient with classic PKU

Compound het with severe mutation, and classic pku PubMed:9860305

PM2

Extremely low in ExAC and 1000 genomes

1.2% Japanese PubMed:9860305

PM3

Compound het with severe mutation

Compound het with severe mutation, showed 8% activity, and classic pku PubMed:9860305

Curation History

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