chr17-42780880-G-A
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2
The NM_032387.5(WNK4):c.182G>A(p.Arg61His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000635 in 1,605,322 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00036 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000032 ( 0 hom. )
Consequence
WNK4
NM_032387.5 missense
NM_032387.5 missense
Scores
4
7
8
Clinical Significance
Conservation
PhyloP100: 3.54
Genes affected
WNK4 (HGNC:14544): (WNK lysine deficient protein kinase 4) This gene encodes a member of the WNK family of serine-threonine protein kinases. The kinase is part of the tight junction complex in kidney cells, and regulates the balance between NaCl reabsorption and K(+) secretion. The kinase regulates the activities of several types of ion channels, cotransporters, and exchangers involved in electrolyte flux in epithelial cells. Mutations in this gene result in pseudohypoaldosteronism type IIB.[provided by RefSeq, Sep 2009]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0802052).
BP6
?
Variant 17-42780880-G-A is Benign according to our data. Variant chr17-42780880-G-A is described in ClinVar as [Benign]. Clinvar id is 2064466.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 50 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WNK4 | NM_032387.5 | c.182G>A | p.Arg61His | missense_variant | 1/19 | ENST00000246914.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WNK4 | ENST00000246914.10 | c.182G>A | p.Arg61His | missense_variant | 1/19 | 1 | NM_032387.5 | P1 | |
WNK4 | ENST00000591448.5 | c.182G>A | p.Arg61His | missense_variant, NMD_transcript_variant | 1/18 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000329 AC: 50AN: 152174Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
50
AN:
152174
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000147 AC: 34AN: 231522Hom.: 0 AF XY: 0.000109 AC XY: 14AN XY: 128048
GnomAD3 exomes
AF:
AC:
34
AN:
231522
Hom.:
AF XY:
AC XY:
14
AN XY:
128048
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000323 AC: 47AN: 1453030Hom.: 0 Cov.: 31 AF XY: 0.0000249 AC XY: 18AN XY: 723238
GnomAD4 exome
AF:
AC:
47
AN:
1453030
Hom.:
Cov.:
31
AF XY:
AC XY:
18
AN XY:
723238
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000361 AC: 55AN: 152292Hom.: 1 Cov.: 32 AF XY: 0.000336 AC XY: 25AN XY: 74456
GnomAD4 genome
?
AF:
AC:
55
AN:
152292
Hom.:
Cov.:
32
AF XY:
AC XY:
25
AN XY:
74456
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
1
ESP6500EA
AF:
AC:
0
ExAC
?
AF:
AC:
16
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 15, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
N
PrimateAI
Pathogenic
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
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