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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000277.3(PAH):c.190del (p.His64fs)

CA229477

102621 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: f10d88ae-ed9a-4e0a-be7e-4f5089438071

HGVS expressions

NM_000277.3:c.190del

NM_000277.3(PAH):c.190del (p.His64fs)

NM_000277.1:c.190del

NM_000277.2:c.190del

NM_001354304.1:c.190del

NM_001354304.2:c.190del

ENST00000307000.7:c.175del

ENST00000546844.1:c.190del

ENST00000548677.2:n.277del

ENST00000548928.1:n.112del

ENST00000549111.5:n.286del

ENST00000550978.6:n.174del

ENST00000551337.5:c.190del

ENST00000551988.5:n.279del

ENST00000553106.5:c.190del

ENST00000635500.1:n.158del

NC_000012.12:g.102894899del

CM000674.2:g.102894899del

NC_000012.11:g.103288677del

CM000674.1:g.103288677del

NC_000012.10:g.101812807del

NG_008690.1:g.27706del

NG_008690.2:g.68514del

Pathogenic

PP4_Moderate PM2 PVS1

PM3

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The frameshift variant c.190del generates a stop codon at residue 72 in exon 3 of 13 and is predicted to undergo NMD. The variant is absent from population databases, including gnomAD. It has been reported heterozygous in at least one PKU patient (PMID: 23271928). In summary, this variant meets criteria to be classified as Pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PP4_moderate.

PP4_Moderate

Patient 25 of PMID: 23271928 is a PKU patient, with blood phenylalanine concentrations > 20 mg/dL. Urinary pterin analysis and blood neopterin dihydropteridine reductase assays were used to exclude tetrahydrobiopterin deficiency.

PubMed:23271928

PM2

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

PVS1

The c.190del frameshift generates a stop codon at residue 72 in exon 3 of 13 and is predicted to undergo NMD.

PM3

Patient 25 was reported as heterozygous for c.190del, however a second variant was not identified.

Approved on: 2020-10-30

Published on: 2020-10-30

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