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]

Variant: NM_000277.3(PAH):c.1048T>A (p.Ser350Thr)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA229304

102494 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: b924ccb3-a7dd-467c-a8d4-f7f78a645076

Approved on: 2021-02-16

Published on: 2021-06-09

HGVS expressions

NM_000277.3:c.1048T>A

NM_000277.3(PAH):c.1048T>A (p.Ser350Thr)

NC_000012.12:g.102844353A>T

CM000674.2:g.102844353A>T

NC_000012.11:g.103238131A>T

CM000674.1:g.103238131A>T

NC_000012.10:g.101762261A>T

NG_008690.1:g.78250T>A

NG_008690.2:g.119058T>A

ENST00000553106.6:c.1048T>A

ENST00000307000.7:c.1033T>A

ENST00000549247.6:n.807T>A

ENST00000551114.2:n.710T>A

ENST00000553106.5:c.1048T>A

ENST00000635477.1:n.152T>A

ENST00000635528.1:n.563T>A

NM_000277.1:c.1048T>A

NM_000277.2:c.1048T>A

NM_001354304.1:c.1048T>A

NM_001354304.2:c.1048T>A

Likely Pathogenic

PP4_Moderate PM5 PM2 PP3

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1048T>A (p.Ser350Thr) variant in PAH has been reported in 1 individual with classic PKU and BH4 deficiency excluded (PMID: 9634518). This variant is absent in population databases. Computational evidence supports a deleterious effect. A different pathogenic missense change (p.Ser350Tyr) has been seen at the same amino acid. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PM5, PP3.

PP4_Moderate

Identified in one patient with Classic PKU, BH4 deficiency excluded. PMID: 9634518

Identified in one patient with Classic PKU, but listed as unclassified. PubMed:9634518

PM5

P350Y classified as pathogenic on ClinVar (Var ID: 102495)

PM2

Absent in controls in ExAC,1000 Genomes or ESP.

PP3

Pedicted deleterious by SIFT, Polyphen, MutationTaster

Curation History

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