Variant 17-42795422-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032387.5(WNK4):c.2962-39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00641 in 1,614,160 control chromosomes in the GnomAD database, including 492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0092 ( 71 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 421 hom. )

Consequence

WNK4
NM_032387.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.480

Variant links:

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]

WNK4 links:

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]

COA3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 17-42795422-C-T is Benign according to our data. Variant chr17-42795422-C-T is described in ClinVar as [Benign]. Clinvar id is 1297227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNK4	NM_032387.5 linkuse as main transcript	c.2962-39C>T		intron_variant		ENST00000246914.10	NP_115763.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNK4	ENST00000246914.10 linkuse as main transcript	c.2962-39C>T	intron_variant		1	NM_032387.5	ENSP00000246914	P1	Q96J92-1
WNK4	ENST00000591448.5 linkuse as main transcript	c.*1463-39C>T	intron_variant, NMD_transcript_variant		1		ENSP00000467088
WNK4	ENST00000587745.1 linkuse as main transcript	c.71-203C>T	intron_variant		5		ENSP00000467312
COA3	ENST00000586680.1 linkuse as main transcript	c.*874G>A	3_prime_UTR_variant, NMD_transcript_variant	3/3	2		ENSP00000467546

Frequencies

GnomAD3 genomes

AF:

0.00928

AC:

1412

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0120

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.160

Gnomad SAS

AF:

0.0124

Gnomad FIN

AF:

0.0137

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000808

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0190

AC:

4786

AN:

251440

Hom.:

275

AF XY:

0.0172

AC XY:

2341

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00221

Gnomad AMR exome

AF:

0.0293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.168

Gnomad SAS exome

AF:

0.00617

Gnomad FIN exome

AF:

0.0126

Gnomad NFE exome

AF:

0.00103

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.00611

AC:

8935

AN:

1461884

Hom.:

421

Cov.:

AF XY:

0.00607

AC XY:

4416

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.0281

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.130

Gnomad4 SAS exome

AF:

0.00704

Gnomad4 FIN exome

AF:

0.0132

Gnomad4 NFE exome

AF:

0.000413

Gnomad4 OTH exome

AF:

0.0120

GnomAD4 genome

AF:

0.00925

AC:

1408

AN:

152276

Hom.:

Cov.:

AF XY:

0.0102

AC XY:

761

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00272

Gnomad4 AMR

AF:

0.0122

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.160

Gnomad4 SAS

AF:

0.0120

Gnomad4 FIN

AF:

0.0137

Gnomad4 NFE

AF:

0.000809

Gnomad4 OTH

AF:

0.0113

Alfa

AF:

0.00356

Hom.:

Bravo

AF:

0.0101

Asia WGS

AF:

0.0580

AC:

201

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 20, 2021	This variant is associated with the following publications: (PMID: 15309683) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.64

DANN

Benign

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over