Variant rs762119830 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004070.4(CLCNKA):c.1613G>A(p.Arg538His) variant causes a missense change. The variant allele was found at a frequency of 0.0000123 in 1,460,906 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R538C) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CLCNKA
NM_004070.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.60

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CLCNKA	NM_004070.4 linkuse as main transcript	c.1613G>A	p.Arg538His	missense_variant	15/20	ENST00000331433.5
CLCNKA	NM_001042704.2 linkuse as main transcript	c.1613G>A	p.Arg538His	missense_variant	15/20
CLCNKA	NM_001257139.2 linkuse as main transcript	c.1484G>A	p.Arg495His	missense_variant	14/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLCNKA	ENST00000331433.5 linkuse as main transcript	c.1613G>A	p.Arg538His	missense_variant	15/20	1	NM_004070.4	P4	P51800-1
CLCNKA	ENST00000375692.5 linkuse as main transcript	c.1613G>A	p.Arg538His	missense_variant	16/21	1		A1	P51800-3
CLCNKA	ENST00000439316.6 linkuse as main transcript	c.1484G>A	p.Arg495His	missense_variant	14/19	2			P51800-2
CLCNKA	ENST00000464764.5 linkuse as main transcript	n.2217G>A		non_coding_transcript_exon_variant	19/24	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000280

AC:

AN:

249834

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135382

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1460906

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726762

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000330

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.092

.;.;T

Eigen

Uncertain

0.34

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.037

MetaRNN

Uncertain

0.69

D;D;D

MetaSVM

Uncertain

0.41

MutationAssessor

Pathogenic

2.9

M;.;M

MutationTaster

Benign

0.78

N;N;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.77

N;N;N

REVEL

Uncertain

0.44

Sift

Benign

0.11

T;T;T

Sift4G

Benign

0.098

T;T;T

Polyphen

1.0

.;.;D

Vest4

0.58

MutPred

0.47

Gain of sheet (P = 0.0166);.;Gain of sheet (P = 0.0166);

MVP

0.86

MPC

0.85

ClinPred

0.86

GERP RS

3.9

Varity_R

0.094

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over