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_000277.2(PAH):c.164T>C (p.Phe55Ser)

CA267639

120266 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: cd7b08c0-d1ff-4dc6-95f5-142a0fb35f8b

Approved on: 2018-12-10

Published on: 2019-04-06

HGVS expressions

NM_000277.2:c.164T>C

NM_000277.2(PAH):c.164T>C (p.Phe55Ser)

NC_000012.12:g.102912795A>G

CM000674.2:g.102912795A>G

NC_000012.11:g.103306573A>G

CM000674.1:g.103306573A>G

NC_000012.10:g.101830703A>G

NG_008690.1:g.9808T>C

NG_008690.2:g.50616T>C

NM_000277.1:c.164T>C

NM_001354304.1:c.164T>C

NM_000277.3:c.164T>C

ENST00000307000.7:c.149T>C

ENST00000546844.1:c.164T>C

ENST00000548677.2:n.251T>C

ENST00000548928.1:n.86T>C

ENST00000549111.5:n.260T>C

ENST00000550978.6:n.148T>C

ENST00000551337.5:c.164T>C

ENST00000551988.5:n.253T>C

ENST00000553106.5:c.164T>C

ENST00000635500.1:n.132T>C

Likely Pathogenic

PM2 PM3 PP3 PP4

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.164T>C (p.Phe55Ser) variant in PAH is reported in 1 French patient with classic PKU. BH4 deficiency was not assessed. It was detected with a known pathogenic variant c.1066-11G>A (PMID: 26666653). This variant is absent from ExAC, gnomAD, 1000G, and ESP. A deleterious effect is predicted in SIFT, Polyphen-2, MutationTaster, and REVEL=0.96. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM3, PP4, PP3.

PM2

Absent from ExAC, gnomAD, 1000G, ESP

PM3

Detected with c.1066-11G>A, PMID: 26666653

Patient genotype: c. [164T>C]; [1066-11G>A]. PubMed:26666653

PP3

Deleterious effect predicted in SIFT, Polyphen2, MutationTaster. REVEL=0.96

PP4

Identified in 1 French patient with classic PKU. BH4 deficiency not assessed. PMID: 26666653

Phe55Ser identified in 1 patient with classic PKU. A total of 364 hyperphenylalaninemic patients, including 42 siblings, were investigated. They represented mixed origin people from 20 French Centers for Inborn Errors of Metabolism. According to their blood Phenylalanine concentration at time of diagnosis, these patients were assigned to one of the three phenotype categories. classical phenylketonuria (cPKU, Phe > 1200 μmol/L). PubMed:26666653

PM5

F55L P/LP

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