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_000277.2(PAH):c.912+3A>C

CA267685

120293 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: a7a70556-f120-4931-8975-e94740d31d25

HGVS expressions

NM_000277.2:c.912+3A>C

NM_000277.2(PAH):c.912+3A>C

NC_000012.12:g.102851684T>G

CM000674.2:g.102851684T>G

NC_000012.11:g.103245462T>G

CM000674.1:g.103245462T>G

NC_000012.10:g.101769592T>G

NG_008690.1:g.70919A>C

NG_008690.2:g.111727A>C

NM_000277.1:c.912+3A>C

NM_001354304.1:c.912+3A>C

NM_000277.3:c.912+3A>C

ENST00000307000.7:c.897+3A>C

ENST00000549247.6:n.671+3A>C

ENST00000551114.2:n.574+3A>C

ENST00000553106.5:c.912+3A>C

ENST00000635477.1:n.73+3A>C

Uncertain Significance

PM2 PP3

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.912+3A>C variant in PAH has not been reported in the medical literature to the best of our knowledge. This variant is absent from gnomAD and the ESP population databases. This is an intronic variant in a highly conserved nucleotide, and computational analyses (Alamut v.2.11) predict that this variant may impact splicing by reducing (~30%) the canonical donor splice site. Given the absence of clinical information and mRNA functional studies, the significance of the c.912+3A>C variant can not be determined with certainty. PAH-specific ACMG/AMP criteria applied: PP3, PM2.

PM2

absent from gnomAD

PP3

Overall reduction of splicing at the donor site ~30%.

Approved on: 2019-11-08

Published on: 2019-11-08

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