Variant X-48966826-T-C 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_004979.6(KCND1):c.1303A>G(p.Ile435Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,203,241 control chromosomes in the GnomAD database, including 1 homozygotes. There are 763 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., 25 hem., cov: 21)

Exomes 𝑓: 0.0021 ( 1 hom. 738 hem. )

Consequence

KCND1
NM_004979.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.53

Variant links:

Genes affected

KCND1 (HGNC:6237): (potassium voltage-gated channel subfamily D member 1) This gene encodes a multipass membrane protein that comprises the pore subunit of the voltage-gated A-type potassium channel, which functions in the repolarization of membrane action potentials. Activity of voltage-gated potassium channels is important in a number of physiological processes, among them the regulation of neurotransmitter release, heart rate, insulin secretion, and smooth muscle contraction. [provided by RefSeq, Aug 2013]

KCND1 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=0.02339378).

BP6

Variant X-48966826-T-C is Benign according to our data. Variant chrX-48966826-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 731747.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 25 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCND1	NM_004979.6 linkuse as main transcript	c.1303A>G	p.Ile435Val	missense_variant	3/6	ENST00000218176.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCND1	ENST00000218176.4 linkuse as main transcript	c.1303A>G	p.Ile435Val	missense_variant	3/6	1	NM_004979.6	P1	Q9NSA2-1
KCND1	ENST00000376477.5 linkuse as main transcript	c.172A>G	p.Ile58Val	missense_variant	2/5	2			Q9NSA2-2

Frequencies

GnomAD3 genomes

AF:

0.00150

AC:

163

AN:

108685

Hom.:

Cov.:

AF XY:

0.000807

AC XY:

AN XY:

30977

show subpopulations

Gnomad AFR

AF:

0.000537

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00130

Gnomad ASJ

AF:

0.00190

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00244

Gnomad OTH

AF:

0.000687

GnomAD3 exomes

AF:

0.00115

AC:

207

AN:

180188

Hom.:

AF XY:

0.00131

AC XY:

AN XY:

64998

show subpopulations

Gnomad AFR exome

AF:

0.000684

Gnomad AMR exome

AF:

0.00103

Gnomad ASJ exome

AF:

0.00138

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000691

Gnomad NFE exome

AF:

0.00186

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00213

AC:

2330

AN:

1094502

Hom.:

Cov.:

AF XY:

0.00205

AC XY:

738

AN XY:

360340

show subpopulations

Gnomad4 AFR exome

AF:

0.000379

Gnomad4 AMR exome

AF:

0.00111

Gnomad4 ASJ exome

AF:

0.000728

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00258

Gnomad4 OTH exome

AF:

0.00209

GnomAD4 genome

AF:

0.00149

AC:

162

AN:

108739

Hom.:

Cov.:

AF XY:

0.000805

AC XY:

AN XY:

31041

show subpopulations

Gnomad4 AFR

AF:

0.000536

Gnomad4 AMR

AF:

0.00130

Gnomad4 ASJ

AF:

0.00190

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00242

Gnomad4 OTH

AF:

0.000678

Alfa

AF:

0.00179

Hom.:

Bravo

AF:

0.00142

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00173

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00119

AC:

ExAC

AF:

0.00110

AC:

133

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.030

CADD

Benign

DANN

Uncertain

1.0

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.97

D;D

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.023

T;T

MetaSVM

Uncertain

0.64

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.88

N;N

REVEL

Uncertain

0.42

Sift

Benign

0.038

D;D

Sift4G

Benign

0.093

T;T

Polyphen

0.25

.;B

Vest4

0.21

MVP

0.83

MPC

0.054

ClinPred

0.036

GERP RS

5.7

Varity_R

0.29

gMVP

0.83

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over