rs3738298

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004980.5(KCND3):c.1269+15C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 1,613,558 control chromosomes in the GnomAD database, including 19,222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2121 hom., cov: 32)

Exomes 𝑓: 0.15 ( 17101 hom. )

Consequence

KCND3
NM_004980.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.440

Publications

7 publications found

Variant links:

Genes affected

KCND3 (HGNC:6239): (potassium voltage-gated channel subfamily D member 3) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shal-related subfamily, members of which form voltage-activated A-type potassium ion channels and are prominent in the repolarization phase of the action potential. This member includes two isoforms with different sizes, which are encoded by alternatively spliced transcript variants of this gene. [provided by RefSeq, Jul 2008]

KCND3 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: G2P
spinocerebellar ataxia type 19/22
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, Ambry Genetics
Brugada syndrome 9
Inheritance: AD Classification: LIMITED Submitted by: Genomics England PanelApp
Brugada syndrome 1
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

KCND3 links:

LOC124904312 (HGNC:):

LOC124904312 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-111786929-G-T is Benign according to our data. Variant chr1-111786929-G-T is described in ClinVar as Benign. ClinVar VariationId is 259600.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004980.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KCND3	NM_001378969.1	MANE Select	c.1269+15C>A	intron	N/A	NP_001365898.1
KCND3	NM_004980.5		c.1269+15C>A	intron	N/A	NP_004971.2
KCND3	NM_001378970.1		c.1269+15C>A	intron	N/A	NP_001365899.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
KCND3	ENST00000302127.5	TSL:5 MANE Select	c.1269+15C>A	intron	N/A	ENSP00000306923.4
KCND3	ENST00000315987.6	TSL:1	c.1269+15C>A	intron	N/A	ENSP00000319591.2
KCND3	ENST00000369697.5	TSL:1	c.1269+15C>A	intron	N/A	ENSP00000358711.1

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25253

AN:

152000

Hom.:

2119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.212

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.147

Gnomad OTH

AF:

0.158

GnomAD2 exomes

AF:

0.162

AC:

40826

AN:

251250

AF XY:

0.166

show subpopulations

Gnomad AFR exome

AF:

0.188

Gnomad AMR exome

AF:

0.116

Gnomad ASJ exome

AF:

0.151

Gnomad EAS exome

AF:

0.204

Gnomad FIN exome

AF:

0.197

Gnomad NFE exome

AF:

0.147

Gnomad OTH exome

AF:

0.154

GnomAD4 exome

AF:

0.150

AC:

219214

AN:

1461440

Hom.:

17101

Cov.:

AF XY:

0.152

AC XY:

110725

AN XY:

727032

show subpopulations

African (AFR)

AF:

0.195

AC:

6534

AN:

33470

American (AMR)

AF:

0.115

AC:

5129

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

3936

AN:

26132

East Asian (EAS)

AF:

0.213

AC:

8450

AN:

39696

South Asian (SAS)

AF:

0.215

AC:

18518

AN:

86236

European-Finnish (FIN)

AF:

0.198

AC:

10569

AN:

53382

Middle Eastern (MID)

AF:

0.141

AC:

794

AN:

5648

European-Non Finnish (NFE)

AF:

0.140

AC:

155871

AN:

1111794

Other (OTH)

AF:

0.156

AC:

9413

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

10293

20586

30880

41173

51466

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5606

11212

16818

22424

28030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.166

AC:

25258

AN:

152118

Hom.:

2121

Cov.:

AF XY:

0.170

AC XY:

12671

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.190

AC:

7876

AN:

41456

American (AMR)

AF:

0.139

AC:

2128

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

522

AN:

3470

East Asian (EAS)

AF:

0.212

AC:

1097

AN:

5174

South Asian (SAS)

AF:

0.212

AC:

1022

AN:

4824

European-Finnish (FIN)

AF:

0.200

AC:

2116

AN:

10588

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.147

AC:

10007

AN:

67992

Other (OTH)

AF:

0.158

AC:

334

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1070

2140

3210

4280

5350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

276

552

828

1104

1380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.152

Hom.:

8010

Bravo

AF:

0.158

Asia WGS

AF:

0.204

AC:

713

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

not provided (1)

Spinocerebellar ataxia type 19/22 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.3

(source)

DANN

Benign

0.60

PhyloP100

0.44

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over