rs397509409

chr12-896627-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_213655.5(WNK1):c.6896G>A(p.Ser2299Asn) 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 (no stars).

• Frequency: Genomes: not found (cov: 28)
• Consequence: WNK1 NM_213655.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.50

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, WNK1
• BP4: Computational evidence support a benign effect (MetaRNN=0.2574309).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNK1	NM_213655.5	c.6896G>A	p.Ser2299Asn	missense_variant	24/28	ENST00000340908.9
WNK1	NM_018979.4	c.6140G>A	p.Ser2047Asn	missense_variant	24/28	ENST00000315939.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNK1	ENST00000340908.9	c.6896G>A	p.Ser2299Asn	missense_variant	24/28	5	NM_213655.5	A2
WNK1	ENST00000315939.11	c.6140G>A	p.Ser2047Asn	missense_variant	24/28	1	NM_018979.4	P2

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 28

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Variant of unknown significance Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Jun 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.093	T;.;T;.;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.26	T;T;T;T;T
MetaSVM	Benign	-0.43	T
MutationTaster	Benign	0.95	D;D;D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.9	N;.;N;.;N
REVEL	Benign	0.17
Sift	Benign	0.078	T;.;T;.;T
Sift4G	Benign	0.080	T;.;D;D;D
Polyphen		0.18	B;.;B;.;.
Vest4		0.59
MutPred		0.11		.;.;Loss of phosphorylation at S2047 (P = 0.0097);.;.;
MVP		0.19
MPC		0.54
ClinPred		0.79	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.24
gMVP		0.060

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

Other links and lift over

dbSNP: rs397509409; hg19: chr12-1005793;