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]

Variant: NM_000277.3:c.443G>A

CA16020790

Gene: PAH (HGNC:5053)

Condition: phenylketonuria (MONDO:0009861)

Inheritance Mode: Autosomal recessive inheritance

UUID: ca00cb65-08c6-4727-ade1-dd87efb4f578

Approved on: 2020-01-26

Published on: 2020-01-26

HGVS expressions

NM_000277.3:c.443G>A

NC_000012.12:g.102866662C>T

CM000674.2:g.102866662C>T

NC_000012.11:g.103260440C>T

CM000674.1:g.103260440C>T

NC_000012.10:g.101784570C>T

NG_008690.1:g.55941G>A

NG_008690.2:g.96749G>A

NM_000277.1:c.443G>A

NM_000277.2:c.443G>A

NM_001354304.1:c.443G>A

ENST00000307000.7:c.428G>A

ENST00000549111.5:n.539G>A

ENST00000551988.5:n.530+10800G>A

ENST00000553106.5:c.443G>A

Likely Pathogenic

PP4_Moderate PP3 PM2 PM3_Supporting

Evidence Links 2

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.443G>A (p.Gly148Asp) variant in PAH has been reported in multiple individuals with PKU (BH4 deficiency excluded). (PMID: 21147011, 15589814). This variant is absent in population databases (PM2). This variant was detected with pathogenic variant IVS4nt5G>T (c.441+5G>T). Computational evidence supports a deleterious effect. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PM3_supporting, PP3.

PP4_Moderate

Detected on 2 alleles. Sequencing of the PAH gene and genes of the BH4 synthesis/ recycling pathways were performed. PMID: 21147011

PubMed:21147011

PubMed:15589814

PP3

Predicted deleterious in SIFT, PolyPhen2, MutationTaster, REVEL=0.944

PM2

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

PM3_Supporting

Detected with IVS4nt5G>T (c.441+5G>T) pathogenic 5 submitters PMID: 15589814

Curation History

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