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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CA16020924

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: c586a0d4-d1d6-4054-91ff-a32183bdbbce

HGVS expressions

NM_000277.3:c.1066-12del

NC_000012.12:g.102843792del

CM000674.2:g.102843792del

NC_000012.11:g.103237570del

CM000674.1:g.103237570del

NC_000012.10:g.101761700del

NG_008690.1:g.78812del

NG_008690.2:g.119620del

NM_000277.1:c.1066-12del

NM_000277.2:c.1066-12del

NM_001354304.1:c.1066-12del

ENST00000307000.7:c.1051-12del

ENST00000549247.6:n.825-12del

ENST00000551114.2:n.728-12del

ENST00000553106.5:c.1066-12del

ENST00000635477.1:n.170-12del

ENST00000635528.1:n.581-12del

Uncertain Significance

BP4 PM2 PP4_Moderate

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

This c.1066-12delT (IVS10-12delT) variant in PAH was reported in one Chinese patient with PAH deficiency (PMID: 26503515). DHPR activity, biopterin and/or pteridine analysis was performed to rule out other causes of hyperphenylalaninemia. This variant is absent from the population databases ExAC and gnomAD. This non-coding variant is not located in a splice region and is not predicted to have splice-altering consequences. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP4, BP4.

BP4

This variant is not located in a splice region and is not predicted to have splice-altering consequences. According to in silico splicing predictions, no significant splicing motif alterations were detected and this mutation probably has no impact on splicing (Human Splicing Finder).

PM2

Absent from population databases gnomAD and ExAC.

PP4_Moderate

This variant was documented once in a SouthernChinese patient diagnosed with PAH deficiency (PMID: 26503515).

This variant was documented once in a Southern Chinese patient diagnosed with PAH deficiency (PMID: 26503515). The patient was a compound heterozygote for the variant, however the 2nd allele was not specified. Subjects in this study were diagnosed through neonatal screening program or by clinical presentation. Phenylalanine plasma concentrations >120 µmol/L were reported for all subjects. Tetrahydrobiopterin (BH4) deficiency was excluded through a BH4 loading test, urinary pterin analysis, DHPR activity assay. PubMed:26503515

Approved on: 2019-11-06

Published on: 2019-11-06

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