Variant 1-16023922-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004070.4(CLCNKA):c.223G>T(p.Val75Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000791 in 1,614,092 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00041 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00083 ( 20 hom. )

Consequence

CLCNKA
NM_004070.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.52

Variant links:

Genes affected

CLCNKA (HGNC:2026): (chloride voltage-gated channel Ka) This gene is a member of the CLC family of voltage-gated chloride channels. The encoded protein is predicted to have 12 transmembrane domains, and requires a beta subunit called barttin to form a functional channel. It is thought to function in salt reabsorption in the kidney and potassium recycling in the inner ear. The gene is highly similar to CLCNKB, which is located 10 kb downstream from this gene. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CLCNKA links:

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=0.01260379).

BP6

Variant 1-16023922-G-T is Benign according to our data. Variant chr1-16023922-G-T is described in ClinVar as [Benign]. Clinvar id is 2638352.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-16023922-G-T is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 20 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CLCNKA	NM_004070.4 linkuse as main transcript	c.223G>T	p.Val75Phe	missense_variant	3/20	ENST00000331433.5	NP_004061.3
CLCNKA	NM_001042704.2 linkuse as main transcript	c.223G>T	p.Val75Phe	missense_variant	3/20		NP_001036169.1
CLCNKA	NM_001257139.2 linkuse as main transcript	c.223G>T	p.Val75Phe	missense_variant	3/19		NP_001244068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLCNKA	ENST00000331433.5 linkuse as main transcript	c.223G>T	p.Val75Phe	missense_variant	3/20	1	NM_004070.4	ENSP00000332771	P4	P51800-1

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00179

AC:

449

AN:

251418

Hom.:

AF XY:

0.00244

AC XY:

331

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0134

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000831

AC:

1215

AN:

1461756

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

862

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.000842

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0120

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000683

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.000407

AC:

AN:

152336

Hom.:

Cov.:

AF XY:

0.000644

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000201

Hom.:

Bravo

AF:

0.000140

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00201

AC:

244

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000178

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

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2022

CLCNKA: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.12

.;.;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.53

T;T;T

MetaRNN

Benign

0.013

T;T;T

MetaSVM

Uncertain

-0.14

MutationAssessor

Uncertain

2.1

M;M;M

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.5

N;N;N

REVEL

Uncertain

0.42

Sift

Benign

0.30

T;D;T

Sift4G

Benign

0.50

T;D;T

Polyphen

0.40

.;.;B

Vest4

0.63

MVP

0.85

MPC

0.47

ClinPred

0.062

GERP RS

1.4

Varity_R

0.10

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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