Variant X-48966649-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004979.6(KCND1):c.1396C>G(p.Leu466Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,207,813 control chromosomes in the GnomAD database, including 58 homozygotes. There are 3,960 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 4 hom., 212 hem., cov: 23)

Exomes 𝑓: 0.011 ( 54 hom. 3748 hem. )

Consequence

KCND1
NM_004979.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.16

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007024437).

BP6

Variant X-48966649-G-C is Benign according to our data. Variant chrX-48966649-G-C is described in ClinVar as [Benign]. Clinvar id is 777742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCND1	NM_004979.6 linkuse as main transcript	c.1396C>G	p.Leu466Val	missense_variant	4/6	ENST00000218176.4	NP_004970.3	Q9NSA2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KCND1	ENST00000218176.4 linkuse as main transcript	c.1396C>G	p.Leu466Val	missense_variant	4/6	1	NM_004979.6	ENSP00000218176.3	Q9NSA2-1
KCND1	ENST00000376477.5 linkuse as main transcript	c.265C>G	p.Leu89Val	missense_variant	3/5	2		ENSP00000365660.1	Q9NSA2-2
KCND1	ENST00000419374.1 linkuse as main transcript	c.109C>G	p.Leu37Val	missense_variant	1/2	3		ENSP00000413989.1	H7C3V4

Frequencies

GnomAD3 genomes

AF:

0.00729

AC:

808

AN:

110890

Hom.:

Cov.:

AF XY:

0.00641

AC XY:

212

AN XY:

33086

show subpopulations

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00578

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00136

Gnomad MID

AF:

0.00424

Gnomad NFE

AF:

0.0119

Gnomad OTH

AF:

0.0109

GnomAD3 exomes

AF:

0.00668

AC:

1202

AN:

179818

Hom.:

AF XY:

0.00654

AC XY:

422

AN XY:

64496

show subpopulations

Gnomad AFR exome

AF:

0.00109

Gnomad AMR exome

AF:

0.00386

Gnomad ASJ exome

AF:

0.00797

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00163

Gnomad FIN exome

AF:

0.00152

Gnomad NFE exome

AF:

0.0116

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.0107

AC:

11786

AN:

1096869

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

3748

AN XY:

362313

show subpopulations

Gnomad4 AFR exome

AF:

0.00159

Gnomad4 AMR exome

AF:

0.00382

Gnomad4 ASJ exome

AF:

0.00744

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.00137

Gnomad4 FIN exome

AF:

0.00208

Gnomad4 NFE exome

AF:

0.0129

Gnomad4 OTH exome

AF:

0.0102

GnomAD4 genome

AF:

0.00728

AC:

808

AN:

110944

Hom.:

Cov.:

AF XY:

0.00640

AC XY:

212

AN XY:

33150

show subpopulations

Gnomad4 AFR

AF:

0.00203

Gnomad4 AMR

AF:

0.00577

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00136

Gnomad4 NFE

AF:

0.0119

Gnomad4 OTH

AF:

0.0107

Alfa

AF:

0.00966

Hom.:

195

Bravo

AF:

0.00774

TwinsUK

AF:

0.0108

AC:

ALSPAC

AF:

0.0135

AC:

ESP6500AA

AF:

0.00183

AC:

ESP6500EA

AF:

0.0119

AC:

ExAC

AF:

0.00705

AC:

856

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

5.8

DANN

Benign

0.96

DEOGEN2

Benign

0.39

.;T

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.56

T;T

MetaRNN

Benign

0.0070

T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.8

.;L

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.70

N;N

REVEL

Benign

0.23

Sift

Benign

0.20

T;T

Sift4G

Benign

0.39

T;T

Polyphen

0.0

.;B

Vest4

0.044

MVP

0.64

MPC

0.054

ClinPred

0.0097

GERP RS

4.8

Varity_R

0.095

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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