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.1027T>G (p.Tyr343Asp)

CA229280

102476 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: fc07dc52-569c-4021-87b5-e54628c440f9

HGVS expressions

NM_000277.3:c.1027T>G

NM_000277.3(PAH):c.1027T>G (p.Tyr343Asp)

NC_000012.12:g.102844374A>C

CM000674.2:g.102844374A>C

NC_000012.11:g.103238152A>C

CM000674.1:g.103238152A>C

NC_000012.10:g.101762282A>C

NG_008690.1:g.78229T>G

NG_008690.2:g.119037T>G

NM_000277.1:c.1027T>G

NM_000277.2:c.1027T>G

NM_001354304.1:c.1027T>G

NM_001354304.2:c.1027T>G

ENST00000307000.7:c.1012T>G

ENST00000549247.6:n.786T>G

ENST00000551114.2:n.689T>G

ENST00000553106.5:c.1027T>G

ENST00000635477.1:n.131T>G

ENST00000635528.1:n.542T>G

Likely Pathogenic

PM3 PM2 PP3 PP4_Moderate

PM5

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1027T>G (p.Tyr343Asp) variant in PAH has been reported in 1 individual with mild PKU (BH4 deficiency excluded) detected in trans with p.S349P (PMID: 27121329). This variant is absent in population databases. Computational evidence supports a deleterious effect. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PM3, PP3.

PM3

Seen in trans with S349P, pathogenic/likely pathogenic in Clinvar (Var ID: 615). Segregation analysis was done to rule out the presence of large genomic rearrangements. PMID: 27121329

Seen in trans with S349P, pathogenic/likely pathogenic in Clinvar (Var ID: 615) PubMed:27121329

PM2

absent from controls.

PP3

Predicted deleterious by MutationTaster, SIFT, Polyphen2.

PP4_Moderate

Seen in a patient with mPKU, not BH4 responsive. The current cutoff value for Phe is 120 μM. A defect in the synthesis or regeneration pathways of 6R-BH4 was ruled out by analyzing urinary pterin levels as well as by measuring the dihydropteridine reductase activity. PMID: 27121329

Seen in a patient with mPKU, not BH4 responsive. PubMed:27121329

PM5

Y343C classified as likely pathogenic

Approved on: 2020-06-01

Published on: 2020-06-01

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.