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_001354304.2:c.843T>A

CA481331323

Gene: PAH (HGNC:5053)

Condition: phenylketonuria (MONDO:0009861)

Inheritance Mode: Autosomal recessive inheritance

UUID: 4b514f05-21fc-449b-beed-8af547df60ef

Approved on: 2022-12-09

Published on: 2022-12-09

HGVS expressions

NM_001354304.2:c.843T>A

NC_000012.12:g.102851756A>T

CM000674.2:g.102851756A>T

NC_000012.11:g.103245534A>T

CM000674.1:g.103245534A>T

NC_000012.10:g.101769664A>T

NG_008690.1:g.70847T>A

NG_008690.2:g.111655T>A

ENST00000553106.6:c.843T>A

ENST00000307000.7:c.828T>A

ENST00000549247.6:n.602T>A

ENST00000551114.2:n.505T>A

ENST00000553106.5:c.843T>A

ENST00000635477.1:n.4T>A

NM_000277.1:c.843T>A

NM_000277.2:c.843T>A

NM_001354304.1:c.843T>A

NM_000277.3:c.843T>A

Uncertain Significance

PM3_Supporting BP7 PP4 PM2

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

This c.843T>A (p.Pro281Pro) variant in PAH was detected with the pathogenic variant c.168+5G>C in a patient with PKU (PMID:26413448). This variant was absent in population databases. This is a synonymous variant which is not predicted to have a splice-altering consequence. In summary, this variant meets criteria to be classified as a variant of unknown significance for PAH. PAH-specific ACMG/AMP criteria applied: BP7, PM3_Supporting, PM2, PP4.

PM3_Supporting

This variant was detected with pathogenic variant c.168+5G>C in a patient with PKU (PMID: 26413448). points=0.5.

BP7

Synonymous variant which is not predicted to have a splice-altering consequence. Multiple in-silico prediction tools classify this variant as benign. SpliceAI score=0.06, dbscSNV Ada score=0, RF score =0.01, TraP score =0.305

PP4

Variant was detected in 1 patients affected with PKU. Genomic DNA was isolated from the leukocytes in blood samples using a DNA purification Qiagen kit. This was seen in trans with pathogenic variants listed in ClinVar. PMID: 26413448

PM2

This variant is absent from population databases gnomAD and ExAC.

Curation History

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