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

CA1139532543

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: a9663fba-c9a0-4f07-a25c-47b3c6a0dac5

HGVS expressions

NM_001354304.2:c.706+5G>A

NM_000277.1:c.706+5G>A

NM_000277.2:c.706+5G>A

NM_001354304.1:c.706+5G>A

NM_000277.3:c.706+5G>A

ENST00000307000.7:c.691+5G>A

ENST00000549111.5:n.807G>A

ENST00000553106.5:c.706+5G>A

NC_000012.12:g.102855131C>T

CM000674.2:g.102855131C>T

NC_000012.11:g.103248909C>T

CM000674.1:g.103248909C>T

NC_000012.10:g.101773039C>T

NG_008690.1:g.67472G>A

NG_008690.2:g.108280G>A

Uncertain Significance

PP4_Moderate PP3 PM2

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

This c.706+5G>A variant in PAH was reported in one patient with hyperphenylalaninemia. Tetrahydrobiopterin deficiency was ruled out with urinary pterin analysis and a DHPR activity assay (PMID: 29499199). This variant is absent from population databases. Multiple lines of computation evidence support a deleterious effect. In summary, this variant meets criteria to be classified as Uncertain Significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP4_moderate, and PP3.

PP4_Moderate

This variant is observed in one patient with HPA (exact Phe level unknown). Tetrahydrobiopterin deficiency was ruled out with urinary pterin analysis and a DHPR activity assay. PMID: 29499199

PubMed:29499199

PP3

Multiple lines of computation evidence support a deleterious effect. Splice AI predicts splice-altering (0.97) and TrAP predicts damaging (0.898 > 99th percentile).

PM2

This variant is absent from gnomAD, ExAC, and 1000 Genomes population databases.

Approved on: 2020-10-15

Published on: 2020-10-15

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.