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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Variant: NM_000277.3(PAH):c.1021A>T (p.Lys341Ter)

CA229272

102470 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 83a0c192-3b59-4e0d-95de-e711ebb17cde

HGVS expressions

NM_000277.3:c.1021A>T

NM_000277.3(PAH):c.1021A>T (p.Lys341Ter)

NC_000012.12:g.102844380T>A

CM000674.2:g.102844380T>A

NC_000012.11:g.103238158T>A

CM000674.1:g.103238158T>A

NC_000012.10:g.101762288T>A

NG_008690.1:g.78223A>T

NG_008690.2:g.119031A>T

ENST00000553106.6:c.1021A>T

ENST00000307000.7:c.1006A>T

ENST00000549247.6:n.780A>T

ENST00000551114.2:n.683A>T

ENST00000553106.5:c.1021A>T

ENST00000635477.1:n.125A>T

ENST00000635528.1:n.536A>T

NM_000277.1:c.1021A>T

NM_000277.2:c.1021A>T

NM_001354304.1:c.1021A>T

NM_001354304.2:c.1021A>T

Pathogenic

PVS1 PM3_Supporting PP4 PM2

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1021A>T (p.Lys341Ter) nonsense variant occurs in exon 10 of 13 and is predicted to result in NMD. It absent from population databases, including gnomAD. It has been reported in at least one patient with cPKU (PMID: 9452062), compound heterozygous with R408W c.1315+1G>A (ClinVar 576, Pathogenic reviewed by PAH VCEP). In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PM3_supporting, PP4.

PVS1

The c.1021A>T (p.Lys341Ter) nonsense variant occurs in exon 10 of 13 and is predicted to result in NMD.

PM3_Supporting

Patient 429 of PMID: 9452062 is compound heterozygous for K341X and c.1315+1G>A (ClinVar 576, Pathogenic reviewed by PAH expert panel). Confirmation of trans phase was not reported.

PP4

Patient 429 of PMID: 9452062 has classical PKU with PHE >1,200 µmol/L.

PM2

The variant is absent from population databases, including gnomAD, ExAC, 1000 Genomes, and ESP.

Approved on: 2022-06-12

Published on: 2022-06-12

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