Variant X-48966182-A-C 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_004979.6(KCND1):c.1591T>G(p.Ser531Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00318 in 1,209,390 control chromosomes in the GnomAD database, including 76 homozygotes. There are 1,059 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 34 hom., 524 hem., cov: 23)

Exomes 𝑓: 0.0018 ( 42 hom. 535 hem. )

Consequence

KCND1
NM_004979.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.86

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047756433).

BP6

Variant X-48966182-A-C is Benign according to our data. Variant chrX-48966182-A-C is described in ClinVar as [Benign]. Clinvar id is 781549.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCND1	NM_004979.6 link	c.1591T>G	p.Ser531Ala	missense_variant	5/6	ENST00000218176.4	NP_004970.3	Q9NSA2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KCND1	ENST00000218176.4 link	c.1591T>G	p.Ser531Ala	missense_variant	5/6	1	NM_004979.6	ENSP00000218176.3	Q9NSA2-1
KCND1	ENST00000376477.5 link	c.460T>G	p.Ser154Ala	missense_variant	4/5	2		ENSP00000365660.1	Q9NSA2-2
KCND1	ENST00000419374.1 link	c.304T>G	p.Ser102Ala	missense_variant	2/2	3		ENSP00000413989.1	H7C3V4

Frequencies

GnomAD3 genomes

AF:

0.0164

AC:

1860

AN:

113149

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

521

AN XY:

35291

show subpopulations

Gnomad AFR

AF:

0.0561

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00702

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000354

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00417

Gnomad NFE

AF:

0.000225

Gnomad OTH

AF:

0.0157

GnomAD3 exomes

AF:

0.00467

AC:

831

AN:

177870

Hom.:

AF XY:

0.00304

AC XY:

194

AN XY:

63846

show subpopulations

Gnomad AFR exome

AF:

0.0580

Gnomad AMR exome

AF:

0.00240

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000542

Gnomad FIN exome

AF:

0.000130

Gnomad NFE exome

AF:

0.000139

Gnomad OTH exome

AF:

0.00300

GnomAD4 exome

AF:

0.00181

AC:

1981

AN:

1096188

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

535

AN XY:

362248

show subpopulations

Gnomad4 AFR exome

AF:

0.0608

Gnomad4 AMR exome

AF:

0.00322

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000149

Gnomad4 FIN exome

AF:

0.0000496

Gnomad4 NFE exome

AF:

0.0000416

Gnomad4 OTH exome

AF:

0.00466

GnomAD4 genome

AF:

0.0165

AC:

1863

AN:

113202

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

524

AN XY:

35354

show subpopulations

Gnomad4 AFR

AF:

0.0561

Gnomad4 AMR

AF:

0.00702

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000355

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000225

Gnomad4 OTH

AF:

0.0155

Alfa

AF:

0.00226

Hom.:

Bravo

AF:

0.0186

ESP6500AA

AF:

0.0511

AC:

196

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00534

AC:

648

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	Labcorp Genetics (formerly Invitae), Labcorp	Dec 20, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.46

.;T

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.54

T;T

MetaRNN

Benign

0.0048

T;T

MetaSVM

Benign

-0.51

MutationAssessor

Benign

1.6

.;L

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.1

N;N

REVEL

Uncertain

0.30

Sift

Benign

0.033

D;D

Sift4G

Benign

0.15

T;T

Polyphen

0.080

.;B

Vest4

0.33

MVP

0.74

MPC

0.052

ClinPred

0.016

GERP RS

5.4

Varity_R

0.23

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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