NM_000277.3(PAH):c.1175T>C (p.Phe392Ser) AND Phenylketonuria

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 31, 2020
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:: RCV001269040.1

Allele description [Variation Report for NM_000277.3(PAH):c.1175T>C (p.Phe392Ser)]

NM_000277.3(PAH):c.1175T>C (p.Phe392Ser)

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.1175T>C (p.Phe392Ser)

HGVS:

NC_000012.12:g.102843670A>G
NG_008690.2:g.119741T>C
NM_000277.3:c.1175T>CMANE SELECT
NM_001354304.2:c.1175T>C
NP_000268.1:p.Phe392Ser
NP_001341233.1:p.Phe392Ser
NC_000012.11:g.103237448A>G
NM_000277.1:c.1175T>C

Protein change:

F392S

Links:

dbSNP: rs199475695

NCBI 1000 Genomes Browser:

rs199475695

Molecular consequence:

NM_000277.3:c.1175T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354304.2:c.1175T>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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001448231	ClinGen PAH Variant Curation Expert Panel	reviewed by expert panel (ClinGen PAH ACMG Specifications v1)	Uncertain significance (Aug 31, 2020)	germline	curation	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001448231

ClinGen PAH Variant Curation Expert Panel

reviewed by expert panel

(ClinGen PAH ACMG Specifications v1)

Uncertain significance
(Aug 31, 2020)

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, SCV001448231.1

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

Description

The c.1175T>C (p.Phe392Ser) variant in PAH was reported in one non-English article that is not accessible (PMID: 22333022). This variant is absent from population databases (PM2), and is predicted deleterious by SIFT, PolyPhen2, MutationTaster, and REVEL = 0.98 (PP3). This variant is same codon as F392I, reported as pathogenic in ClinVar (VarID:852581; 2 submitters) (PM5). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PP3, PM5

#	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: Apr 23, 2022

ClinVar

Relating variation to medicine