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]

x This classification has been retracted/unpublished!

Variant: NM_000277.2(PAH):c.473G>C (p.Arg158Pro)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA229571

102694 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 4e4301cb-1d43-4b70-9923-1aceceb5a6cf

Approved on: 2018-12-10

Published on: 2019-11-08

HGVS expressions

NM_000277.2:c.473G>C

NM_000277.2(PAH):c.473G>C (p.Arg158Pro)

NC_000012.12:g.102866632C>G

CM000674.2:g.102866632C>G

NC_000012.11:g.103260410C>G

CM000674.1:g.103260410C>G

NC_000012.10:g.101784540C>G

NG_008690.1:g.55971G>C

NG_008690.2:g.96779G>C

ENST00000553106.6:c.473G>C

ENST00000307000.7:c.458G>C

ENST00000549111.5:n.569G>C

ENST00000551988.5:n.530+10830G>C

ENST00000553106.5:c.473G>C

NM_000277.1:c.473G>C

NM_001354304.1:c.473G>C

NM_000277.3:c.473G>C

NM_001354304.2:c.473G>C

Likely Pathogenic

PP3 PP4 PM3 PM5 PM2

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.473G>C (p.Arg158Pro) variant in PAH was reported in a patient with Mild Hyperphenylalaninemia (Phenylalanine level 380 umol/l) PMID: 8659548. It was detected with V388M (known pathogenic variant). It has an extremely low frequency in ExAC and gnomAD (MAF 0.00002). It is predicted deleterious in SIFT, Polyphen2, MutationTaster and REVEL=0.98. Two different pathogenic missense changes at this amino acid have been seen before (R158W, R158Q). In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM3, PM5, PP3, PP4.

PP3

Predicted deleterious in SIFT, Polyphen2, MutationTaster. REVEL=0.98

PP4

D145V is reported in a patient with MHP, Phenylalanine level 380 umol/l. PMID: 8659548

D145V is reported on 1 allele in a patient with MHP, Phenylalanine level 380 umol/l. PubMed:8659548

PM3

D145V is detected with V388M (VarID 619, Pathogenic) PMID: 8659548

D145V is reported on 1 allele with V388M (VarID 619, Pathogenic) on allele 2 in a patient with MHP. PubMed:8659548

PM5

R158W and R158Q Pathogenic in ClinVar

PM2

Extremely low frequency in ExAC, gnomAD: MAF 0.00002

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.