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

CA16020723

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: ae0b08c5-e096-49c2-b3eb-72983fca1c76

HGVS expressions

NM_000277.1:c.60+5G>C

NC_000012.12:g.102917066C>G

CM000674.2:g.102917066C>G

NC_000012.11:g.103310844C>G

CM000674.1:g.103310844C>G

NC_000012.10:g.101834974C>G

NG_008690.1:g.5537G>C

NG_008690.2:g.46345G>C

NM_000277.2:c.60+5G>C

NM_001354304.1:c.60+5G>C

NM_000277.3:c.60+5G>C

NM_001354304.2:c.60+5G>C

ENST00000307000.7:c.-88+5G>C

ENST00000546844.1:c.60+5G>C

ENST00000547319.1:n.371+5G>C

ENST00000549111.5:n.156+5G>C

ENST00000550978.6:n.44+5G>C

ENST00000551337.5:c.60+5G>C

ENST00000551988.5:n.149+5G>C

ENST00000553106.5:c.60+5G>C

ENST00000635500.1:n.29-4168G>C

Pathogenic

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"

PP3 PP4 PM2

PM5

Evidence Links 1

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.60+5G>C variant in PAH has been reported in a cohort of Germany PKU/HPA patients (PMID: 10394930) This variant is absent in population databases. Multiple lines of computational evidence support a deleterious effect. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PP4, PM2, PP3.

PP3

Alamut Visual v.2.7.1 on 4/4/2017: Splicing predictions at nearest natural junction Predicted change at donor site 5 bps upstream: -35.9% MaxEnt: -31.9% NNSPLICE: -63.5% HSF: -12.4%

PP4

PMID 10394930: Table 1, listed 2 alleles of this c.60+5G>C variants in a cohort of Germany PKU/HPA patients.

Table 1, listed 4 alleles of this c.60+5G>C variants in a cohort of Germany PKU/HPA patients. PubMed:10394930

PM2

Absent from controls in ExAC, gnomAD, 1000 Genomes, ESP

PM5

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Approved on: 2020-06-04

Published on: 2020-06-04

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