chrX-54198490-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The ENST00000354646.7(WNK3):c.5237C>T(p.Ala1746Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000232 in 1,163,175 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000094 ( 0 hom., 1 hem., cov: 21)

Exomes 𝑓: 0.000025 ( 0 hom. 9 hem. )

Consequence

WNK3
ENST00000354646.7 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.234

Publications

3 publications found

Variant links:

Genes affected

WNK3 (HGNC:14543): (WNK lysine deficient protein kinase 3) This gene encodes a protein belonging to the 'with no lysine' family of serine-threonine protein kinases. These family members lack the catalytic lysine in subdomain II, and instead have a conserved lysine in subdomain I. This family member functions as a positive regulator of the transcellular Ca2+ transport pathway, and it plays a role in the increase of cell survival in a caspase-3-dependent pathway. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

WNK3 Gene-Disease associations (from GenCC):

Prieto syndrome
Inheritance: XL Classification: MODERATE Submitted by: G2P

WNK3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07699776).

BP6

Variant X-54198490-G-A is Benign according to our data. Variant chrX-54198490-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3905027.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
WNK3	NM_020922.5 link	c.5237C>T	p.Ala1746Val	missense_variant	Exon 24 of 24	NP_065973.2	Q9BYP7-1
WNK3	NM_001002838.4 link	c.5066C>T	p.Ala1689Val	missense_variant	Exon 23 of 23	NP_001002838.1	Q9BYP7-3
WNK3	NM_001395166.1 link	c.5066C>T	p.Ala1689Val	missense_variant	Exon 23 of 23	NP_001382095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNK3	ENST00000354646.7 link	c.5237C>T	p.Ala1746Val	missense_variant	Exon 24 of 24	1		ENSP00000346667.2		Q9BYP7-1
WNK3	ENST00000375169.7 link	c.5066C>T	p.Ala1689Val	missense_variant	Exon 23 of 23	5		ENSP00000364312.3		Q9BYP7-3

Frequencies

GnomAD3 genomes

AF:

0.00000938

AC:

AN:

106591

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000434

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000329

AC:

AN:

182434

AF XY:

0.0000448

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1056536

Hom.:

Cov.:

AF XY:

0.0000263

AC XY:

AN XY:

342598

show subpopulations

African (AFR)

AF:

0.0000787

AC:

AN:

25424

American (AMR)

AF:

0.00

AC:

AN:

34999

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19061

East Asian (EAS)

AF:

0.0000334

AC:

AN:

29904

South Asian (SAS)

AF:

0.000133

AC:

AN:

52776

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40379

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4038

European-Non Finnish (NFE)

AF:

0.0000161

AC:

AN:

805316

Other (OTH)

AF:

0.0000672

AC:

AN:

44639

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000938

AC:

AN:

106639

Hom.:

Cov.:

AF XY:

0.0000336

AC XY:

AN XY:

29751

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29273

American (AMR)

AF:

0.00

AC:

AN:

9673

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2584

East Asian (EAS)

AF:

0.00

AC:

AN:

3365

South Asian (SAS)

AF:

0.000436

AC:

AN:

2294

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5244

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

51877

Other (OTH)

AF:

0.00

AC:

AN:

1443

Alfa

AF:

0.000198

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000550

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

WNK3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.88

CADD

Benign

5.8

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.066

.;T;T;.

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.58

T;T;.;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.077

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N;N;.

PhyloP100

0.23

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.1

N;N;N;.

REVEL

Benign

0.014

Sift

Benign

0.049

D;D;D;.

Sift4G

Benign

0.27

T;T;T;T

Polyphen

0.0

B;B;B;.

Vest4

0.16

MutPred

0.34

.;Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);.;

MVP

0.082

MPC

0.21

ClinPred

0.041

GERP RS

2.6

Varity_R

0.066

gMVP

0.21

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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chrX-54198490-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over