chrX-54198365-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000354646.7(WNK3):c.5362T>C(p.Ser1788Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000373 in 1,206,844 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., 4 hem., cov: 22)

Exomes 𝑓: 0.000032 ( 0 hom. 13 hem. )

Consequence

WNK3
ENST00000354646.7 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0330

Publications

0 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028395921).

BP6

Variant X-54198365-A-G is Benign according to our data. Variant chrX-54198365-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3190676.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
WNK3	NM_020922.5 link	c.5362T>C	p.Ser1788Pro	missense_variant	Exon 24 of 24	NP_065973.2	Q9BYP7-1
WNK3	NM_001002838.4 link	c.5191T>C	p.Ser1731Pro	missense_variant	Exon 23 of 23	NP_001002838.1	Q9BYP7-3
WNK3	NM_001395166.1 link	c.5191T>C	p.Ser1731Pro	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.5362T>C	p.Ser1788Pro	missense_variant	Exon 24 of 24	1		ENSP00000346667.2		Q9BYP7-1
WNK3	ENST00000375169.7 link	c.5191T>C	p.Ser1731Pro	missense_variant	Exon 23 of 23	5		ENSP00000364312.3		Q9BYP7-3

Frequencies

GnomAD3 genomes

AF:

0.0000895

AC:

AN:

111758

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000954

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000671

GnomAD2 exomes

AF:

0.0000506

AC:

AN:

178006

AF XY:

0.0000637

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000112

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000501

Gnomad OTH exome

AF:

0.000229

GnomAD4 exome

AF:

0.0000320

AC:

AN:

1095086

Hom.:

Cov.:

AF XY:

0.0000360

AC XY:

AN XY:

360672

show subpopulations

African (AFR)

AF:

0.000152

AC:

AN:

26386

American (AMR)

AF:

0.000114

AC:

AN:

35033

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19260

East Asian (EAS)

AF:

0.00

AC:

AN:

30161

South Asian (SAS)

AF:

0.0000188

AC:

AN:

53296

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40419

Middle Eastern (MID)

AF:

0.00218

AC:

AN:

4122

European-Non Finnish (NFE)

AF:

0.0000190

AC:

AN:

840422

Other (OTH)

AF:

0.0000217

AC:

AN:

45987

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000895

AC:

AN:

111758

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

33942

show subpopulations

African (AFR)

AF:

0.0000325

AC:

AN:

30765

American (AMR)

AF:

0.0000954

AC:

AN:

10482

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2644

East Asian (EAS)

AF:

0.00

AC:

AN:

3571

South Asian (SAS)

AF:

0.00

AC:

AN:

2661

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6052

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

53168

Other (OTH)

AF:

0.000671

AC:

AN:

1491

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Aug 02, 2021

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.97

CADD

Benign

7.2

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.052

.;T;T;.

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.50

T;T;.;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.028

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.46

.;N;N;.

PhyloP100

-0.033

PrimateAI

Benign

0.31

PROVEAN

Benign

1.2

N;N;N;.

REVEL

Benign

0.070

Sift

Benign

1.0

T;T;T;.

Sift4G

Benign

0.19

T;T;T;T

Polyphen

0.0

B;B;B;.

Vest4

0.090

MutPred

0.037

.;Gain of phosphorylation at T1786 (P = 0.177);Gain of phosphorylation at T1786 (P = 0.177);.;

MVP

0.043

MPC

0.27

ClinPred

0.43

GERP RS

-0.46

Varity_R

0.061

gMVP

0.18

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chrX-54198365-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over