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]

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CA16020975

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: d334616b-19a0-4ae3-8973-719fb1d2cc2b

HGVS expressions

NM_001354304.2:c.1235T>G

NM_000277.1:c.1235T>G

NM_000277.2:c.1235T>G

NM_001354304.1:c.1235T>G

NM_000277.3:c.1235T>G

ENST00000307000.7:c.1220T>G

ENST00000551114.2:n.897T>G

ENST00000553106.5:c.1235T>G

ENST00000635477.1:n.339T>G

ENST00000635528.1:n.750T>G

NC_000012.12:g.102840480A>C

CM000674.2:g.102840480A>C

NC_000012.11:g.103234258A>C

CM000674.1:g.103234258A>C

NC_000012.10:g.101758388A>C

NG_008690.1:g.82123T>G

NG_008690.2:g.122931T>G

Uncertain Significance

PM2 PM3_Supporting PP3 PP4

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1235T>G (p.Val412Gly) variant in PAH meets criteria to be classified as uncertain significance due to insufficient evidence. PAH-specific ACMG/AMP criteria applied: PM2: Absent from population databases (1000 Genomes, ExAC). PP3: Computational prediction tools suggest that the c.1235T>G variant is damaging to protein function. Evolutionarily conserved. PP4: Patient has classic PKU (PMID:24350308). PM3_Supporting: Found to co-occur with p.R408W in one patient with classic PKU, but no additional studies to demonstrate phase of variants. No other PAH variants identified in patient (PMID:24350308). Undefined BH4 responsiveness (PMID:24350308)

PM2

Not present in any databases

PM3_Supporting

Co-occured with p.R408W in patient with classic PKU. No additional studies done to confirm phase of variant.

PP3

Predicted to be damaging with SIFT, PolyPhen, and MutTaster. Conserved evolutionarily (PhyloP30way, SiPhy).

PP4

Patient has classic PKU, phenotype not further specified

PubMed:24350308

Approved on: 2020-06-25

Published on: 2020-06-25

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