NM_018979.4:c.2656C>T

Variant names:

• chr12-879855-C-T
• rs569121553
• NM_018979.4:c.2656C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018979.4(WNK1):​c.2656C>T​(p.Pro886Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: WNK1 NM_018979.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.63

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17004603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNK1	NM_018979.4	c.2656C>T	p.Pro886Ser	missense_variant	Exon 11 of 28	ENST00000315939.11	NP_061852.3
WNK1	NM_213655.5	c.3867+1494C>T		intron_variant	Intron 12 of 27	ENST00000340908.9	NP_998820.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNK1	ENST00000315939.11	c.2656C>T	p.Pro886Ser	missense_variant	Exon 11 of 28	1	NM_018979.4	ENSP00000313059.6
WNK1	ENST00000340908.9	c.3867+1494C>T		intron_variant	Intron 12 of 27	5	NM_213655.5	ENSP00000341292.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000795 AC: 2 AN: 251428 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135884

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461892 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	.;T;.
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;M;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.3	.;N;D
REVEL	Benign	0.028
Sift	Uncertain	0.0020	.;D;D
Sift4G	Benign	0.069	.;T;T
Polyphen		0.39	.;B;.
Vest4		0.29
MutPred		0.31		.;Gain of relative solvent accessibility (P = 0.0023);.;
MVP		0.11
MPC		0.57
ClinPred		0.58	D
GERP RS		4.8
Varity_R		0.11

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: rs569121553; hg19: chr12-989021;