NM_006005.3(WFS1):c.1371G>T (p.Arg457Ser) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 20, 2016
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000603890.7

Allele description [Variation Report for NM_006005.3(WFS1):c.1371G>T (p.Arg457Ser)]

NM_006005.3(WFS1):c.1371G>T (p.Arg457Ser)

Gene:

WFS1:wolframin ER transmembrane glycoprotein [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4p16.1

Genomic location:

Preferred name:

NM_006005.3(WFS1):c.1371G>T (p.Arg457Ser)

HGVS:

NC_000004.12:g.6301166G>T
NG_011700.1:g.36317G>T
NM_001145853.1:c.1371G>T
NM_006005.3:c.1371G>TMANE SELECT
NP_001139325.1:p.Arg457Ser
NP_005996.2:p.Arg457Ser
LRG_1417t1:c.1371G>T
LRG_1417:g.36317G>T
LRG_1417p1:p.Arg457Ser
NC_000004.11:g.6302893G>T
O76024:p.Arg457Ser

Protein change:

R457S

Links:

UniProtKB: O76024#VAR_029502; dbSNP: rs113446173

NCBI 1000 Genomes Browser:

rs113446173

Molecular consequence:

NM_001145853.1:c.1371G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_006005.3:c.1371G>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000711250	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Jun 20, 2016)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15605410, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000711250

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Jun 20, 2016)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Wolfram syndrome in French population: characterization of novel mutations and polymorphisms in the WFS1 gene.

Giuliano F, Bannwarth S, Monnot S, Cano A, Chabrol B, Vialettes B, Delobel B, Paquis-Flucklinger V; French Group of WS.

Hum Mutat. 2005 Jan;25(1):99-100.

PubMed [citation]

PMID:: 15605410

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000711250.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

The p.Arg457Ser variant in WFS1 has been reported in one individual with atypica l Wolfram syndrome (Giuliano 2005). However, a variant affecting the remaining c opy of WFS1 was not identified in this individual, and a dominant family history of hearing loss was not described. This variant has been identified in 0.06% (3 9/66642) of European chromosomes by the Exome Aggregation Consortium (ExAC, http ://exac.broadinstitute.org; dbSNP rs113446173); however, its frequency is not hi gh enough to rule out a pathogenic role. Computational prediction tools and cons ervation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain.

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

Last Updated: Jan 19, 2025

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