NM_018979.4(WNK1):c.3188C>T (p.Thr1063Ile) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 26, 2023
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:: RCV003323505.2

Allele description [Variation Report for NM_018979.4(WNK1):c.3188C>T (p.Thr1063Ile)]

NM_018979.4(WNK1):c.3188C>T (p.Thr1063Ile)

Gene:

WNK1:WNK lysine deficient protein kinase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12p13.33

Genomic location:

Preferred name:

NM_018979.4(WNK1):c.3188C>T (p.Thr1063Ile)

HGVS:

NC_000012.12:g.881768C>T
NG_007984.3:g.133710C>T
NM_001184985.2:c.3968C>T
NM_014823.3:c.2447C>T
NM_018979.4:c.3188C>TMANE SELECT
NM_213655.5:c.3944C>T
NP_001171914.1:p.Thr1323Ile
NP_055638.2:p.Thr816Ile
NP_061852.3:p.Thr1063Ile
NP_998820.3:p.Thr1315Ile
NP_998820.3:p.Thr1315Ile
LRG_247t1:c.3188C>T
LRG_247t2:c.3944C>T
LRG_247:g.133710C>T
LRG_247p1:p.Thr1063Ile
LRG_247p2:p.Thr1315Ile
NC_000012.11:g.990934C>T
NM_018979.3:c.3188C>T
NM_213655.4:c.3944C>T

Protein change:

T1063I

Links:

dbSNP: rs201379287

NCBI 1000 Genomes Browser:

rs201379287

Molecular consequence:

NM_001184985.2:c.3968C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_014823.3:c.2447C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_018979.4:c.3188C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_213655.5:c.3944C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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
SCV004029592	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jul 26, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004029592

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jul 26, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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	clinical testing

Citations

PubMed

Integration of whole genome sequencing into a healthcare setting: high diagnostic rates across multiple clinical entities in 3219 rare disease patients.

Stranneheim H, Lagerstedt-Robinson K, Magnusson M, Kvarnung M, Nilsson D, Lesko N, Engvall M, Anderlid BM, Arnell H, Johansson CB, Barbaro M, Björck E, Bruhn H, Eisfeldt J, Freyer C, Grigelioniene G, Gustavsson P, Hammarsjö A, Hellström-Pigg M, Iwarsson E, Jemt A, Laaksonen M, et al.

Genome Med. 2021 Mar 17;13(1):40. doi: 10.1186/s13073-021-00855-5.

PubMed [citation]

PMID:: 33726816
PMCID:: PMC7968334

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004029592.1

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

Description

Variant summary: WNK1 c.3188C>T (p.Thr1063Ile) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00017 in 251472 control chromosomes, predominantly at a frequency of 0.00035 within the Non-Finnish European subpopulation in the gnomAD database (i.e. in 44 carriers). The high number of carriers in controls suggest that the variant is likely not associated with a dominant, early onset, high penetrance disease phenotype. On th other hand, the variant, c.3188C>T, has been reported in the literature in a homozygous individual, who underwent whole genome sequencing (WGS) however, no phenotype info was provided (Stranneheim_2021). This report does not provide unequivocal conclusions about association of the variant with Neuropathy, Hereditary Sensory and Autonomic, Type 2A. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 33726816). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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 13, 2025

ClinVar

Relating variation to medicine