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.1038del (p.Leu347fs)

CA229295

102487 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 9ecda5f7-ae61-4301-84b1-f07b41fa9c9b

HGVS expressions

NM_000277.3:c.1038del

NM_000277.3(PAH):c.1038del (p.Leu347fs)

NC_000012.12:g.102844365del

CM000674.2:g.102844365del

NC_000012.11:g.103238143del

CM000674.1:g.103238143del

NC_000012.10:g.101762273del

NG_008690.1:g.78240del

NG_008690.2:g.119048del

ENST00000553106.6:c.1038del

ENST00000307000.7:c.1023del

ENST00000549247.6:n.797del

ENST00000551114.2:n.700del

ENST00000553106.5:c.1038del

ENST00000635477.1:n.142del

ENST00000635528.1:n.553del

NM_000277.1:c.1038del

NM_000277.2:c.1038del

NM_001354304.1:c.1038del

NM_001354304.2:c.1038del

Pathogenic

PVS1 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.1038del (p.Leu347fs) variant in PAH has been reported in a Danish PKU patient, serum Phe >600 umol/L; BH4 deficiency excluded (PMID: 8406445; PP4). This frameshift variant is predicted to undergo NMD, not located in last exon or last 50bp of preliminary exon. Coding exon number 10 out of 13 coding exons (10 out of total exons) (PVS1). This variant is absent from population databases (PM2). In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PP4.

PVS1

Frameshift variant, predicted to undergo NMD, not located in last exon or last 50bp of preliminary exon. Coding exon number 10 out of 13 coding exons (10 out of total exons).

PP4

PMID: 8406445 - L347fs detected in a Danish PKU patient, serum Phe >600 umol/L; Other causes of hyperphenylalaninemia ruled out (Guttler, 1980)

PM2

Variant absent from population databases.

Approved on: 2021-10-10

Published on: 2021-12-10

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