chrX-54198355-T-C

Variant names:

• chrX-54198355-T-C
• rs1173270244
• ENST00000354646.7:c.5372A>G

Variant summary

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

The ENST00000354646.7(WNK3):​c.5372A>G​(p.Asn1791Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. N1791N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 22)
• Consequence: WNK3 ENST00000354646.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.58
• 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=0.24332696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNK3	NM_020922.5	c.5372A>G	p.Asn1791Ser	missense_variant	Exon 24 of 24		NP_065973.2
WNK3	NM_001002838.4	c.5201A>G	p.Asn1734Ser	missense_variant	Exon 23 of 23		NP_001002838.1
WNK3	NM_001395166.1	c.5201A>G	p.Asn1734Ser	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.5372A>G	p.Asn1791Ser	missense_variant	Exon 24 of 24	1		ENSP00000346667.2
WNK3	ENST00000375169.7	c.5201A>G	p.Asn1734Ser	missense_variant	Exon 23 of 23	5		ENSP00000364312.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 22

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.5372A>G (p.N1791S) alteration is located in exon 24 (coding exon 23) of the WNK3 gene. This alteration results from a A to G substitution at nucleotide position 5372, causing the asparagine (N) at amino acid position 1791 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.075	.;T;T;.
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	T;T;.;T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	.;M;M;.
PhyloP100		4.6
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.4	N;N;N;.
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D;D;D;.
Sift4G	Benign	0.094	T;T;T;T
Polyphen		0.98	D;P;P;.
Vest4		0.34
MVP		0.31
MPC		0.46
ClinPred		0.91	D
GERP RS		5.4
Varity_R		0.26
gMVP		0.25
Mutation Taster		=96/4	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: rs1173270244; hg19: chrX-54224788;