NM_000277.3(PAH):c.1154T>C (p.Leu385Pro) AND Phenylketonuria

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 13, 2023
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003479540.1

Allele description [Variation Report for NM_000277.3(PAH):c.1154T>C (p.Leu385Pro)]

NM_000277.3(PAH):c.1154T>C (p.Leu385Pro)

Gene:

PAH:phenylalanine hydroxylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q23.2

Genomic location:

Preferred name:

NM_000277.3(PAH):c.1154T>C (p.Leu385Pro)

Other names:

NM_000277.3:c.1154T>C

HGVS:

NC_000012.12:g.102843691A>G
NG_008690.2:g.119720T>C
NM_000277.3:c.1154T>CMANE SELECT
NM_001354304.2:c.1154T>C
NP_000268.1:p.Leu385Pro
NP_001341233.1:p.Leu385Pro
NC_000012.11:g.103237469A>G

Protein change:

L385P

Molecular consequence:

NM_000277.3:c.1154T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354304.2:c.1154T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Phenylketonuria (PKU)
Synonyms:: Phenylketonurias; Oligophrenia phenylpyruvica; Folling disease
Identifiers:: MONDO: MONDO:0009861; MedGen: C0031485; Orphanet: 716; OMIM: 261600

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004222639	ClinGen PAH Variant Curation Expert Panel	reviewed by expert panel (ClinGen PAH ACMG Specifications v1)	Likely pathogenic (Oct 13, 2023)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004222639

ClinGen PAH Variant Curation Expert Panel

reviewed by expert panel

(ClinGen PAH ACMG Specifications v1)

Likely pathogenic
(Oct 13, 2023)

germline

curation

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation

Details of each submission

From ClinGen PAH Variant Curation Expert Panel, SCV004222639.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	not provided

Description

The c.1154T>C (p.Leu385Pro) variant in PAH has been reported in at least 3 Chinese patients with Phe > 120umol/L (BH4 deficiency excluded) (PP4_Moderate; PMIDs:29499199, 23932990). This variant was detected in the homozygous state in two patients (PM3; PMID:23932990). This variant is absent in population databases (PM2). This variant is predicted deleterious by SIFT, PolyPhen, MutationTaster, and REVEL = 0.817 (PP3). In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP4_Moderate, PM3, PP3.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jan 6, 2024

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