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(PAH):c.1155C>G (p.Leu385=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA180265

167413 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 7db6caaf-1261-40a2-b2d0-479d9d546076

Approved on: 2022-12-09

Published on: 2022-12-09

HGVS expressions

NM_000277.3:c.1155C>G

NM_000277.3(PAH):c.1155C>G (p.Leu385=)

NC_000012.12:g.102843690G>C

CM000674.2:g.102843690G>C

NC_000012.11:g.103237468G>C

CM000674.1:g.103237468G>C

NC_000012.10:g.101761598G>C

NG_008690.2:g.119721C>G

ENST00000553106.6:c.1155C>G

ENST00000307000.7:c.1140C>G

ENST00000549247.6:n.914C>G

ENST00000551114.2:n.817C>G

ENST00000553106.5:c.1155C>G

ENST00000635477.1:n.259C>G

ENST00000635528.1:n.670C>G

NM_000277.2:c.1155C>G

NM_001354304.1:c.1155C>G

NM_001354304.2:c.1155C>G

Benign

BA1 BP7

PP4 PM3 PM2

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

This c.1155C>G (p.Leu385=) synonymous variant in PAH is not predicted to have a splice-altering consequence. This variant was present at a high frequency of 0.840256 in 1000 genomes and 0.858145 in ExAC. In summary, this variant meets criteria to be classified as a benign for PAH. PAH-specific ACMG/AMP criteria applied: BP7, BA1.

BA1

Present in European population at frequency of 0.8429 and in all populations at frequency of 0.840256 (1000 genomes). Present in European Non-Finnish population at frequency of 0.847263 and in all populations at frequency of 0.858145(ExAC).

BP7

Synonymous variant which is not predicted to have a splice-altering consequence. Several in-silico prediction tools did not have a classification for this variant (SpliceA, dbscSNV, Ada and RF score). This variant was classified as benign according to TraP (score =0.241).

PP4

This variant was detected in multiple unaffected individuals (PMID: 23856132,20187763, 26413448)

PM3

This variant was detected in trans in multiple unaffected individuals (PMID: 23856132,20187763, 26413448)

PM2

Present in European Non-Finnish population at frequency of 0.856883 and in all populations at frequency of 0.849531 (gnomAD). Present in European Non-Finnish population at frequency of 0.847263 and in all populations at frequency of 0.858145(ExAC). The PM2 threshold set by the PAH Variant Curation Expert Panel (VCEP) is 0.0002.

Curation History

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