17-42795263-C-A
Position:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_032387.5(WNK4):c.2842C>A(p.Leu948Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000188 in 1,613,878 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00020 ( 2 hom. )
Consequence
WNK4
NM_032387.5 missense
NM_032387.5 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: 0.335
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]
COA3 (HGNC:24990): (cytochrome c oxidase assembly factor 3) This gene encodes a member of the cytochrome c oxidase assembly factor family. Studies of a related gene in fly suggest that the encoded protein is localized to mitochondria and is essential for cytochrome c oxidase function. [provided by RefSeq, Nov 2012]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.008671194).
BP6
Variant 17-42795263-C-A is Benign according to our data. Variant chr17-42795263-C-A is described in ClinVar as [Benign]. Clinvar id is 323346.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 15 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WNK4 | NM_032387.5 | c.2842C>A | p.Leu948Ile | missense_variant | 14/19 | ENST00000246914.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WNK4 | ENST00000246914.10 | c.2842C>A | p.Leu948Ile | missense_variant | 14/19 | 1 | NM_032387.5 | P1 | |
WNK4 | ENST00000591448.5 | c.*1343C>A | 3_prime_UTR_variant, NMD_transcript_variant | 13/18 | 1 | ||||
WNK4 | ENST00000587745.1 | c.71-362C>A | intron_variant | 5 | |||||
COA3 | ENST00000586680.1 | c.*1033G>T | 3_prime_UTR_variant, NMD_transcript_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152070Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
15
AN:
152070
Hom.:
Cov.:
31
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: 0.000303 AC: 76AN: 250810Hom.: 0 AF XY: 0.000384 AC XY: 52AN XY: 135568
GnomAD3 exomes
AF:
AC:
76
AN:
250810
Hom.:
AF XY:
AC XY:
52
AN XY:
135568
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: 0.000198 AC: 289AN: 1461688Hom.: 2 Cov.: 35 AF XY: 0.000250 AC XY: 182AN XY: 727126
GnomAD4 exome
AF:
AC:
289
AN:
1461688
Hom.:
Cov.:
35
AF XY:
AC XY:
182
AN XY:
727126
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: 0.0000986 AC: 15AN: 152190Hom.: 0 Cov.: 31 AF XY: 0.000134 AC XY: 10AN XY: 74410
GnomAD4 genome
AF:
AC:
15
AN:
152190
Hom.:
Cov.:
31
AF XY:
AC XY:
10
AN XY:
74410
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:
TwinsUK
AF:
AC:
0
ALSPAC
AF:
AC:
1
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
1
ExAC
AF:
AC:
39
Asia WGS
AF:
AC:
1
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Pseudohypoaldosteronism type 2B Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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