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

Variant: NM_000277.3(PAH):c.163_165del (p.Phe55del)

CA229450

102603 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: b8f27de0-e08a-4c93-ad6a-2192544aaacc

HGVS expressions

NM_000277.3:c.163_165del

NM_000277.3(PAH):c.163_165del (p.Phe55del)

NC_000012.12:g.102912794_102912796del

CM000674.2:g.102912794_102912796del

NC_000012.11:g.103306572_103306574del

CM000674.1:g.103306572_103306574del

NC_000012.10:g.101830702_101830704del

NG_008690.1:g.9807_9809del

NG_008690.2:g.50615_50617del

ENST00000553106.6:c.163_165del

ENST00000307000.7:c.148_150del

ENST00000546844.1:c.163_165del

ENST00000548677.2:n.250_252del

ENST00000548928.1:n.85_87del

ENST00000549111.5:n.259_261del

ENST00000550978.6:n.147_149del

ENST00000551337.5:c.163_165del

ENST00000551988.5:n.252_254del

ENST00000553106.5:c.163_165del

ENST00000635500.1:n.131_133del

NM_000277.1:c.163_165del

NM_000277.2:c.163_165del

NM_001354304.1:c.163_165del

NM_001354304.2:c.163_165del

Likely Pathogenic

PP4 PM3 PM4 PM2

BP3

Evidence Links 0

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

This c.163_165del (p.Phe55del) variant in PAH was detected in trans with the c.168+5G>C and p.Phe39Leu pathogenic variants in multiple individuals with PKU (PMID:28676969, 17513426). This variant is absent in population databases. This in-frame variant is not found in a repetitive region and does not cause a stop-loss. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM3, PP4, PM4

PP4

This variant was detected in multiple individuals affected with PKU (PMID:28676969, 17513426, 27469133)

PM3

This variant was detected in trans with the pathogenic variant c.168+5G>C in a patient with PKU (PMID:27469133) and with the pathogenic variant p.Phe39Leu patient mPKU (PMID: 17513426). points=1.

PM4

This in-frame variant is not found in a repetitive region without a known function. It i does not cause a stop loss variant.

PM2

This variant is absent from population databases gnomAD and ExAC.

BP3

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

Approved on: 2022-12-09

Published on: 2022-12-09

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.