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

Variant: NM_000277.3(PAH):c.1065+3A>C

CA229318

102504 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 8cb4c847-1be8-4234-8519-5a0260d150bc

HGVS expressions

NM_000277.3:c.1065+3A>C

NM_000277.3(PAH):c.1065+3A>C

NC_000012.12:g.102844333T>G

CM000674.2:g.102844333T>G

NC_000012.11:g.103238111T>G

CM000674.1:g.103238111T>G

NC_000012.10:g.101762241T>G

NG_008690.1:g.78270A>C

NG_008690.2:g.119078A>C

NM_000277.1:c.1065+3A>C

NM_000277.2:c.1065+3A>C

NM_001354304.1:c.1065+3A>C

NM_001354304.2:c.1065+3A>C

ENST00000307000.7:c.1050+3A>C

ENST00000549247.6:n.824+3A>C

ENST00000551114.2:n.727+3A>C

ENST00000553106.5:c.1065+3A>C

ENST00000635477.1:n.169+3A>C

ENST00000635528.1:n.580+3A>C

Uncertain Significance

PP3 PM2

PP4

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

(PAH):c.1065+3A>C is an intronic variant that is predicted to be splice altering in multiple lines of computational evidence. This variant was identified in a patient with an unspecified PKU/HPA phenotype. The variant was not specified to be heterozygous or homozygous (PMID 10394930). This variant is absent in population databases. In summary, this variant has insufficient evidence and is classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2 and PP3.

PP3

Predicted splice altering in multiple lines of computational evidence. Splice altering event predicted low by splicing AI (0.59) and predicted deleterious by dbsSNV (1.0) and deleterious in RF (0.95). TraP score greater than 99.9th percentile, predicted deleterious (0.965).

PM2

Absent from GnomAD.

PP4

This variant was identified patient with an unspecified PKU/HPA phenotype. The variant was not specified to be heterozygous or homozygous. Subjects in this study were recruited from pediatric centers in Germany, methodology of diagnosis was not specified (PMID 10394930).

Approved on: 2020-07-30

Published on: 2020-07-30

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