NM_006005.3(WFS1):c.817G>A (p.Glu273Lys) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 9, 2017
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:: RCV000200344.8

Allele description [Variation Report for NM_006005.3(WFS1):c.817G>A (p.Glu273Lys)]

NM_006005.3(WFS1):c.817G>A (p.Glu273Lys)

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.817G>A (p.Glu273Lys)

Other names:

p.E273K:GAG>AAG

HGVS:

NC_000004.12:g.6295145G>A
NG_011700.1:g.30296G>A
NM_001145853.1:c.817G>A
NM_006005.3:c.817G>AMANE SELECT
NP_001139325.1:p.Glu273Lys
NP_005996.2:p.Glu273Lys
LRG_1417t1:c.817G>A
LRG_1417:g.30296G>A
LRG_1417p1:p.Glu273Lys
NC_000004.11:g.6296872G>A

Protein change:

E273K

Links:

dbSNP: rs142428158

NCBI 1000 Genomes Browser:

rs142428158

Molecular consequence:

NM_001145853.1:c.817G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006005.3:c.817G>A - 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
SCV000731650	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (May 9, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26435059, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000731650

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(May 9, 2017)

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

Phenotype Prediction of Pathogenic Nonsynonymous Single Nucleotide Polymorphisms in WFS1.

Qian X, Qin L, Xing G, Cao X.

Sci Rep. 2015 Oct 5;5:14731. doi: 10.1038/srep14731.

PubMed [citation]

PMID:: 26435059
PMCID:: PMC4592972

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, SCV000731650.2

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

Description

The p.Glu273Lys variant in WFS1 has not been previously reported in individuals with hearing loss, but has been reported in ClinVar (Variation ID 215382) as of uncertain significance. It has also been identified in 0.16% (54/34416) of Latin o chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadins titute.org; dbSNP rs142428158). Although this variant has been seen in the gener al population, its frequency is not high enough to rule out a pathogenic role. C omputational prediction tools and conservation analysis do not provide strong su pport for or against an impact to the protein. In summary, the clinical signific ance of the p.Glu273Lys 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: May 16, 2025

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Relating variation to medicine