rs143890340
Positions:
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong
The NM_018979.4(WNK1):c.2290A>C(p.Thr764Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Consequence
WNK1
NM_018979.4 missense
NM_018979.4 missense
Scores
19
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.493
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), WNK1. . Gene score misZ 2.1626 (greater than the threshold 3.09). Trascript score misZ 4.652 (greater than threshold 3.09). GenCC has associacion of gene with neuropathy, hereditary sensory and autonomic, type 2A, hereditary sensory and autonomic neuropathy type 2, pseudohypoaldosteronism type 2C.
BP4
Computational evidence support a benign effect (MetaRNN=0.03209898).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WNK1 | NM_213655.5 | c.3784A>C | p.Thr1262Pro | missense_variant | 12/28 | ENST00000340908.9 | NP_998820.3 | |
WNK1 | NM_018979.4 | c.2290A>C | p.Thr764Pro | missense_variant | 10/28 | ENST00000315939.11 | NP_061852.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WNK1 | ENST00000340908.9 | c.3784A>C | p.Thr1262Pro | missense_variant | 12/28 | 5 | NM_213655.5 | ENSP00000341292.5 | ||
WNK1 | ENST00000315939.11 | c.2290A>C | p.Thr764Pro | missense_variant | 10/28 | 1 | NM_018979.4 | ENSP00000313059.6 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;T;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;N;.;.;.;.
PrimateAI
Benign
T
PROVEAN
Benign
N;.;N;.;N;D;.
REVEL
Benign
Sift
Benign
T;.;D;.;D;T;.
Sift4G
Benign
T;.;T;T;T;T;D
Polyphen
B;.;B;.;.;.;.
Vest4
MutPred
0.11
.;.;Gain of glycosylation at T764 (P = 0.0333);.;.;.;.;
MVP
MPC
0.15
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at