NM_006005.3(WFS1):c.1871T>C (p.Val624Ala) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 14, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000280969.10

Allele description [Variation Report for NM_006005.3(WFS1):c.1871T>C (p.Val624Ala)]

NM_006005.3(WFS1):c.1871T>C (p.Val624Ala)

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.1871T>C (p.Val624Ala)

HGVS:

NC_000004.12:g.6301666T>C
NG_011700.1:g.36817T>C
NM_001145853.1:c.1871T>C
NM_006005.3:c.1871T>CMANE SELECT
NP_001139325.1:p.Val624Ala
NP_005996.2:p.Val624Ala
LRG_1417t1:c.1871T>C
LRG_1417:g.36817T>C
LRG_1417p1:p.Val624Ala
NC_000004.11:g.6303393T>C

Protein change:

V624A

Links:

dbSNP: rs747477628

NCBI 1000 Genomes Browser:

rs747477628

Molecular consequence:

NM_001145853.1:c.1871T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_006005.3:c.1871T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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arginine-glutamic acid dipeptide repeats protein isoform a [Homo sapiens]
arginine-glutamic acid dipeptide repeats protein isoform a [Homo sapiens]
gi|112382216|ref|NP_036234.3|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000343279	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Uncertain significance (Jul 19, 2016)	germline	clinical testing	Citation Link,
SCV002152257	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 14, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17492394, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000343279

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Uncertain significance
(Jul 19, 2016)

germline

clinical testing

Citation Link,

SCV002152257

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 14, 2023)

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	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the WFS1 gene are a frequent cause of autosomal dominant nonsyndromic low-frequency hearing loss in Japanese.

Fukuoka H, Kanda Y, Ohta S, Usami SI.

J Hum Genet. 2007;52(6):510-515. doi: 10.1007/s10038-007-0144-3. Epub 2007 May 11.

PubMed [citation]

PMID:: 17492394

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Eurofins Ntd Llc (ga), SCV000343279.4

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

#	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		1	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002152257.3

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt WFS1 protein function. ClinVar contains an entry for this variant (Variation ID: 289011). This missense change has been observed in individual(s) with non-syndromic sensorineural hearing loss (PMID: 17492394). This variant is present in population databases (rs747477628, gnomAD 0.02%). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 624 of the WFS1 protein (p.Val624Ala).

#	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: Sep 29, 2024

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