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_001354304.2:c.1096C>G

CA386493311

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 5aff9fba-7c15-4ff6-87d5-4d90f4c313fd

HGVS expressions

NM_001354304.2:c.1096C>G

NC_000012.12:g.102843749G>C

CM000674.2:g.102843749G>C

NC_000012.11:g.103237527G>C

CM000674.1:g.103237527G>C

NC_000012.10:g.101761657G>C

NG_008690.1:g.78854C>G

NG_008690.2:g.119662C>G

ENST00000553106.6:c.1096C>G

ENST00000307000.7:c.1081C>G

ENST00000549247.6:n.855C>G

ENST00000551114.2:n.758C>G

ENST00000553106.5:c.1096C>G

ENST00000635477.1:n.200C>G

ENST00000635528.1:n.611C>G

NM_000277.1:c.1096C>G

NM_000277.2:c.1096C>G

NM_001354304.1:c.1096C>G

NM_000277.3:c.1096C>G

Uncertain Significance

PP4 PM3 PM2

PP3 PM5

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

This c.1096C>G (p.Pro366Ala) variant in PAH was seen in a patient with PKU in trans with the likely pathogenic variant p.Gly247Arg (PMID: 28982351). This variant was absent in population databases. Computational evidence is conflicting. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM3, PP4.

PP4

Variant was detected in a patient affected with PKU (plasma Phe >120 umol/L). BH4 cofactor deficiency were excluded using the loading test PMID: 28982351

PM3

This variant was detected in trans with the ClinVar likely pathogenic variant p.Gly247Arg in a patient with PKU (PMID: 28982351). points=1.

PM2

This variant is absent from population databases gnomAD and ExAC

PP3

Multiple lines of conflicting computation evidence predicted as benign in Polyphen, tolerated in Sift and disease causing in MutationTaster. revel score 0.608 also does not support this line of evidence.

PM5

Three other variants one of unknown significance (p.P366L) and two likely pathogenic (p.P366H) and (p.P366S) have been documented in ClinVar at this amino acid residue.

Approved on: 2022-10-14

Published on: 2022-10-14

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