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_000277.3(PAH):c.400C>T (p.Gln134Ter)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA229534

102664 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: a4230842-495a-46b2-84dd-ca3657bb29f4

Approved on: 2022-10-14

Published on: 2022-10-14

HGVS expressions

NM_000277.3:c.400C>T

NM_000277.3(PAH):c.400C>T (p.Gln134Ter)

NC_000012.12:g.102877503G>A

CM000674.2:g.102877503G>A

NC_000012.11:g.103271281G>A

CM000674.1:g.103271281G>A

NC_000012.10:g.101795411G>A

NG_008690.1:g.45100C>T

NG_008690.2:g.85908C>T

ENST00000553106.6:c.400C>T

ENST00000307000.7:c.385C>T

ENST00000549111.5:n.496C>T

ENST00000550978.6:n.384C>T

ENST00000551337.5:c.400C>T

ENST00000551988.5:n.489C>T

ENST00000553106.5:c.400C>T

NM_000277.1:c.400C>T

NM_000277.2:c.400C>T

NM_001354304.1:c.400C>T

NM_001354304.2:c.400C>T

Pathogenic

PVS1 PP4 PM2

PM3

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

This c.400C>T (p.Gln134Ter) variant in PAH was detected in a patient with PKU (PMID:17096675). This variant was absent in population databases. This was predicted as a null variant in PAH where LOF is a known mechanism of disease. This is a nonsense variant in exon 4 of 13 coding exons predicted to undergo nonsense mediated decay. In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1,PM2,PP4.

PVS1

Nonsense variant, predicted to undergo NMD, found in coding exon 4 out of 13 coding exons.

PP4

Variant was detected in a patient with PKU (serum Phe >1200 µM) PMID: 17096675

PM2

This variant is absent from population databases gnomAD and ExAC

PM3

This variant was detected in trans with an unspecified variant in a patient with PKU (PMID: 17096675).

Curation History

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