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_001354304.2:c.703C>T

CA16020845

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: d5850138-93a9-4cf0-a49e-9373a12b1fda

HGVS expressions

NM_001354304.2:c.703C>T

NC_000012.12:g.102855139G>A

CM000674.2:g.102855139G>A

NC_000012.11:g.103248917G>A

CM000674.1:g.103248917G>A

NC_000012.10:g.101773047G>A

NG_008690.1:g.67464C>T

NG_008690.2:g.108272C>T

ENST00000553106.6:c.703C>T

ENST00000307000.7:c.688C>T

ENST00000549111.5:n.799C>T

ENST00000553106.5:c.703C>T

NM_000277.1:c.703C>T

NM_000277.2:c.703C>T

NM_001354304.1:c.703C>T

NM_000277.3:c.703C>T

Pathogenic

PP4 PVS1 PM2

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The NM_000277.3(PAH):c.703C>T (p.Gln235Ter) nonsense variant occurs in exon 6 of 13 and is predicted to result in NMD. It has been reported in one classic PKU patient (http://www.fedoa.unina.it/9088/1/TESI%20DOTTORATO%20ALESSIA%20PALMIERI.pdf) and is found at an extremely low allele frequency in gnomAD (MAF of 0.00006152 in the African/African-American population). In summary, this variant meets criteria to be classified as Pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PP4.

PP4

One classic PKU patient (Phe levels > 1200 mmol/L) has been reported with the Gln235Ter in a dissertation from the University of Naples Federico II (http://www.fedoa.unina.it/9088/1/TESI%20DOTTORATO%20ALESSIA%20PALMIERI.pdf).

PVS1

The nonsense variant Gln235Ter occurs in exon 6 of 13 and is predicted to result in NMD.

PM2

This variant is found at an extremely low allele frequency of 0.000003980 overall in gnomAD with a MAF of 0.00006152 (1/16256) in the African/African-American population.

Approved on: 2020-12-08

Published on: 2022-03-11

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