NM_213655.5:c.1287A>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_213655.5(WNK1):c.1287A>G(p.Ala429Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 1,613,654 control chromosomes in the GnomAD database, including 453,569 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 38465 hom., cov: 31)

Exomes 𝑓: 0.75 ( 415104 hom. )

Consequence

WNK1
NM_213655.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -1.43

Variant links:

Genes affected

WNK1 (HGNC:14540): (WNK lysine deficient protein kinase 1) This gene encodes a member of the WNK subfamily of serine/threonine protein kinases. The encoded protein may be a key regulator of blood pressure by controlling the transport of sodium and chloride ions. Mutations in this gene have been associated with pseudohypoaldosteronism type II and hereditary sensory neuropathy type II. Alternatively spliced transcript variants encoding different isoforms have been described but the full-length nature of all of them has yet to be determined.[provided by RefSeq, May 2010]

WNK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 12-830136-A-G is Benign according to our data. Variant chr12-830136-A-G is described in ClinVar as [Benign]. Clinvar id is 261066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-830136-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.42 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.853 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNK1	NM_213655.5 link	c.1287A>G	p.Ala429Ala	synonymous_variant	Exon 4 of 28	ENST00000340908.9	NP_998820.3	Q9H4A3-5
WNK1	NM_018979.4 link	c.1287A>G	p.Ala429Ala	synonymous_variant	Exon 4 of 28	ENST00000315939.11	NP_061852.3	Q9H4A3-1A5D8Z4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNK1	ENST00000340908.9 link	c.1287A>G	p.Ala429Ala	synonymous_variant	Exon 4 of 28	5	NM_213655.5	ENSP00000341292.5		Q9H4A3-5
WNK1	ENST00000315939.11 link	c.1287A>G	p.Ala429Ala	synonymous_variant	Exon 4 of 28	1	NM_018979.4	ENSP00000313059.6		Q9H4A3-1

Frequencies

GnomAD3 genomes

AF:

0.705

AC:

107067

AN:

151926

Hom.:

38443

Cov.:

show subpopulations

Gnomad AFR

AF:

0.562

Gnomad AMI

AF:

0.868

Gnomad AMR

AF:

0.749

Gnomad ASJ

AF:

0.681

Gnomad EAS

AF:

0.875

Gnomad SAS

AF:

0.697

Gnomad FIN

AF:

0.813

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.752

Gnomad OTH

AF:

0.694

GnomAD3 exomes

AF:

0.750

AC:

188493

AN:

251420

Hom.:

71413

AF XY:

0.750

AC XY:

101917

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.553

Gnomad AMR exome

AF:

0.769

Gnomad ASJ exome

AF:

0.693

Gnomad EAS exome

AF:

0.867

Gnomad SAS exome

AF:

0.711

Gnomad FIN exome

AF:

0.803

Gnomad NFE exome

AF:

0.760

Gnomad OTH exome

AF:

0.721

GnomAD4 exome

AF:

0.752

AC:

1099354

AN:

1461610

Hom.:

415104

Cov.:

AF XY:

0.751

AC XY:

546176

AN XY:

727124

show subpopulations

Gnomad4 AFR exome

AF:

0.558

Gnomad4 AMR exome

AF:

0.768

Gnomad4 ASJ exome

AF:

0.687

Gnomad4 EAS exome

AF:

0.875

Gnomad4 SAS exome

AF:

0.716

Gnomad4 FIN exome

AF:

0.804

Gnomad4 NFE exome

AF:

0.756

Gnomad4 OTH exome

AF:

0.740

GnomAD4 genome

AF:

0.705

AC:

107138

AN:

152044

Hom.:

38465

Cov.:

AF XY:

0.708

AC XY:

52609

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.563

Gnomad4 AMR

AF:

0.749

Gnomad4 ASJ

AF:

0.681

Gnomad4 EAS

AF:

0.875

Gnomad4 SAS

AF:

0.698

Gnomad4 FIN

AF:

0.813

Gnomad4 NFE

AF:

0.752

Gnomad4 OTH

AF:

0.690

Alfa

AF:

0.729

Hom.:

50973

Bravo

AF:

0.696

Asia WGS

AF:

0.735

AC:

2556

AN:

3478

EpiCase

AF:

0.731

EpiControl

AF:

0.737

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Neuropathy, hereditary sensory and autonomic, type 2A

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 12, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Pseudohypoaldosteronism type 2C

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Pseudohypoaldosteronism type 2C;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.46

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over