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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Variant: NM_000277.3(PAH):c.399T>C (p.Asn133=)

CA6748962

729975 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: ec33787a-fb20-4579-8f9c-b7414342be72

Approved on: 2021-07-25

Published on: 2021-07-25

HGVS expressions

NM_000277.3:c.399T>C

NM_000277.3(PAH):c.399T>C (p.Asn133=)

ENST00000553106.6:c.399T>C

ENST00000307000.7:c.384T>C

ENST00000549111.5:n.495T>C

ENST00000550978.6:n.383T>C

ENST00000551337.5:c.399T>C

ENST00000551988.5:n.488T>C

ENST00000553106.5:c.399T>C

NM_000277.1:c.399T>C

NM_000277.2:c.399T>C

NM_001354304.1:c.399T>C

NM_001354304.2:c.399T>C

NC_000012.12:g.102877504A>G

CM000674.2:g.102877504A>G

NC_000012.11:g.103271282A>G

CM000674.1:g.103271282A>G

NC_000012.10:g.101795412A>G

NG_008690.1:g.45099T>C

NG_008690.2:g.85907T>C

Benign

BP7 BS1 BS2

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.399T>C (p.Asn387=) variant in PAH meets criteria to be classified as benign. PAH-specific ACMG/AMP criteria applied: BS1: MAF = 0.00675 which is within the threshold for this expert group. BS7: HSF, Splice AI and TraP predict no significant impact on splicing signals.BS2: Observed in two healthy homozygotes in gnomAd and ExAc.

BP7

Per HSF, there is no significant impact on splicing signals predicted. SpliceAI predicts Benign (0.05). TraP Score is 0.007 (<25%ile, v3).

BS1

MAF = 0.00675. Absent in 1000 Genomes and ESP, MAF = 0.00029 in gnomAD and 0.0003 in ExAC.

BS2

Found in one homozygous Ashkenazi Jewish person in gnomAd, and one homozygous European person in ExAc

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