rs782629234

Variant names:

• chrX-54198512-C-A
• rs782629234
• ENST00000354646.7:c.5215G>T

Your query was ambiguous. Multiple possible variants found:

• chrX-54198512-C-A
• chrX-54198512-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000354646.7(WNK3):​c.5215G>T​(p.Val1739Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,204,205 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1739I) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000092 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: WNK3 ENST00000354646.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.12
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25620872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNK3	NM_020922.5	c.5215G>T	p.Val1739Phe	missense_variant	Exon 24 of 24		NP_065973.2
WNK3	NM_001002838.4	c.5044G>T	p.Val1682Phe	missense_variant	Exon 23 of 23		NP_001002838.1
WNK3	NM_001395166.1	c.5044G>T	p.Val1682Phe	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	c.5215G>T	p.Val1739Phe	missense_variant	Exon 24 of 24	1		ENSP00000346667.2
WNK3	ENST00000375169.7	c.5044G>T	p.Val1682Phe	missense_variant	Exon 23 of 23	5		ENSP00000364312.3

Frequencies

GnomAD3 genomes AF: 0.00000919 AC: 1 AN: 108766 Hom.: 0 Cov.: 22

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: 0.00

Gnomad FIN AF: 0.000178

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000183 AC: 2 AN: 1095439 Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 1 AN XY: 361143

African (AFR) AF: 0.00 AC: 0 AN: 26343

American (AMR) AF: 0.00 AC: 0 AN: 35167

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19360

East Asian (EAS) AF: 0.00 AC: 0 AN: 30173

South Asian (SAS) AF: 0.00 AC: 0 AN: 53929

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4128

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 839843

Other (OTH) AF: 0.00 AC: 0 AN: 45996

GnomAD4 genome AF: 0.00000919 AC: 1 AN: 108766 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 31328

African (AFR) AF: 0.00 AC: 0 AN: 29821

American (AMR) AF: 0.00 AC: 0 AN: 9971

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2619

East Asian (EAS) AF: 0.00 AC: 0 AN: 3464

South Asian (SAS) AF: 0.00 AC: 0 AN: 2430

European-Finnish (FIN) AF: 0.000178 AC: 1 AN: 5618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52488

Other (OTH) AF: 0.00 AC: 0 AN: 1443

Alfa AF: 0.00 Hom.: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.0034	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.099	.;T;T;.
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.79	T;T;.;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.4	.;M;M;.
PhyloP100		2.1
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.7	N;N;N;.
REVEL	Benign	0.099
Sift	Uncertain	0.0010	D;D;D;.
Sift4G	Uncertain	0.018	D;D;D;D
Polyphen		0.99	D;D;D;.
Vest4		0.43
MutPred		0.19		.;Gain of loop (P = 0.2045);Gain of loop (P = 0.2045);.;
MVP		0.22
MPC		0.64
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.54
gMVP		0.46
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs782629234; hg19: chrX-54224945;