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:c.847A>G

CA16020876

Gene: PAH (HGNC:5053)

Condition: phenylketonuria (MONDO:0009861)

Inheritance Mode: Autosomal recessive inheritance

UUID: deb05865-1cb0-4972-95ae-59e2da8df3a4

Approved on: 2018-12-10

Published on: 2019-04-06

HGVS expressions

NM_000277.1:c.847A>G

NC_000012.12:g.102851752T>C

CM000674.2:g.102851752T>C

NC_000012.11:g.103245530T>C

CM000674.1:g.103245530T>C

NC_000012.10:g.101769660T>C

NG_008690.1:g.70851A>G

NG_008690.2:g.111659A>G

NM_000277.2:c.847A>G

NM_001354304.1:c.847A>G

NM_000277.3:c.847A>G

ENST00000307000.7:c.832A>G

ENST00000549247.6:n.606A>G

ENST00000551114.2:n.509A>G

ENST00000553106.5:c.847A>G

ENST00000635477.1:n.8A>G

Likely Pathogenic

PM2 PM5 PM3 PP4_Moderate

PP3

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.847A>G (p.Ile283Val) variant in PAH is absent from all population databases, and is at the same amino acid as a previously established pathogenic variant (c.847A>T (p.Ile283Phe)). It has been identified in a patient with classic PKU (BH4 defect excluded), and in trans with a known pathogenic variant (c.1045T>C, p.Ser349Pro) PMID: 27121329. Summary evidence using PAH specific ACMG/AMP guidelines :PM2, PM5, PM3, PP4_Moderate.

PM2

Absent from all population databases

PM5

NM_000277.2(PAH):c.847A>T (p.Ile283Phe) is LP/P in ClinVar

PM3

In trans with c.1045T>C (p.Ser349Pro) (pathogenic in ClinVar)

In trans with c.1045T>C (p.Ser349Pro) (pathogenic in ClinVar) PubMed:27121329

PP4_Moderate

Single patient with Classic PKU (>1200umol/L), BH4 non-responder. PMID: 27121329

Single patient with BH4 non-responsive Classic PKU PubMed:27121329

PP3

in silico predictors do not agree. REVEL=0.438

Curation History

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