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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CA16020980

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 04c30910-babe-4e4b-a469-d820d4147268

Approved on: 2020-10-29

Published on: 2020-10-29

HGVS expressions

NM_001354304.2:c.1246C>A

NM_000277.1:c.1246C>A

NM_000277.2:c.1246C>A

NM_001354304.1:c.1246C>A

NM_000277.3:c.1246C>A

ENST00000307000.7:c.1231C>A

ENST00000551114.2:n.908C>A

ENST00000553106.5:c.1246C>A

ENST00000635477.1:n.350C>A

ENST00000635528.1:n.761C>A

NC_000012.12:g.102840469G>T

CM000674.2:g.102840469G>T

NC_000012.11:g.103234247G>T

CM000674.1:g.103234247G>T

NC_000012.10:g.101758377G>T

NG_008690.1:g.82134C>A

NG_008690.2:g.122942C>A

Uncertain Significance

PP3 PP4 PM2

PM5

Evidence Links 2

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1246C>A (p.Pro416Thr) variant in PAH has been reported in 1 patient with mild non-PKU HPA with Phe = 246-420umol/L (BH4 deficiency not excluded) (PP4; PMID: 9380432). This variant is absent from population databases (PM2). This variant is predicted to be deleterious by SIFT, PolyPhen2, MutationTaster, and REVEL = 0.965 (PP3). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP3, PP4.

PP3

Predicted deleterious by SIFT, PolyPhen2, MutationTaster, and REVEL = 0.965.

PP4

PMID: 9380432 - P416T detected with mild non-PKU HPA, plasma Phe = 246-420umol/L on unrestricted diet, BH4 deficiency not excluded (number of patients/alleles not specified) - see Figure 1

PubMed:9380432

PubMed:31332730

PM2

Variant absent from population databases.

PM5

c.1246A>T (p.Pro416Gln) curated as VUS by ClinGen PAH VCEP; Also reported as VUS in ClinVar (VarID: 558091)

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