rs185017345

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_004977.3(KCNC3):c.123G>T(p.Gln41His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00878 in 947,006 control chromosomes in the GnomAD database, including 566 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 394 hom., cov: 24)

Exomes 𝑓: 0.0033 ( 172 hom. )

Consequence

KCNC3
NM_004977.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.85

Publications

4 publications found

Variant links:

Genes affected

KCNC3 (HGNC:6235): (potassium voltage-gated channel subfamily C member 3) The Shaker gene family of Drosophila encodes components of voltage-gated potassium channels and is comprised of four subfamilies. Based on sequence similarity, this gene is similar to one of these subfamilies, namely the Shaw subfamily. The protein encoded by this gene belongs to the delayed rectifier class of channel proteins and is an integral membrane protein that mediates the voltage-dependent potassium ion permeability of excitable membranes. Alternate splicing results in several transcript variants. [provided by RefSeq, Mar 2014]

KCNC3 Gene-Disease associations (from GenCC):

spinocerebellar ataxia type 13
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

KCNC3 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 (MetaRNN=0.0013549328).

BP6

Variant 19-50328960-C-A is Benign according to our data. Variant chr19-50328960-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 284725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNC3	NM_004977.3 link	c.123G>T	p.Gln41His	missense_variant	Exon 1 of 5	ENST00000477616.2	NP_004968.2	Q14003
KCNC3	NM_001372305.1 link	c.-106G>T		5_prime_UTR_variant	Exon 1 of 5		NP_001359234.1
KCNC3	NR_110912.2 link	n.68+4509G>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNC3	ENST00000477616.2 link	c.123G>T	p.Gln41His	missense_variant	Exon 1 of 5	1	NM_004977.3	ENSP00000434241.1	Q14003
KCNC3	ENST00000670667.1 link	c.123G>T	p.Gln41His	missense_variant	Exon 1 of 4			ENSP00000499301.1	A0A590UJ62
KCNC3	ENST00000376959.6 link	c.123G>T	p.Gln41His	missense_variant	Exon 1 of 5	5		ENSP00000366158.2	E7ETH1
KCNC3	ENST00000474951.1 link	c.-75+4509G>T		intron_variant	Intron 1 of 3	2		ENSP00000432438.1	E9PQY4

Frequencies

GnomAD3 genomes

AF:

0.0389

AC:

5692

AN:

146148

Hom.:

392

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.000885

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0128

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.0200

GnomAD2 exomes

AF:

0.0345

AC:

AN:

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00326

AC:

2610

AN:

800764

Hom.:

172

Cov.:

AF XY:

0.00299

AC XY:

1159

AN XY:

387448

show subpopulations

African (AFR)

AF:

0.143

AC:

2173

AN:

15232

American (AMR)

AF:

0.0111

AC:

AN:

3508

Ashkenazi Jewish (ASJ)

AF:

0.00118

AC:

AN:

7620

East Asian (EAS)

AF:

0.00

AC:

AN:

12426

South Asian (SAS)

AF:

0.000191

AC:

AN:

20988

European-Finnish (FIN)

AF:

0.00

AC:

AN:

11550

Middle Eastern (MID)

AF:

0.00890

AC:

AN:

1910

European-Non Finnish (NFE)

AF:

0.000158

AC:

110

AN:

697974

Other (OTH)

AF:

0.00873

AC:

258

AN:

29556

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

109

218

328

437

546

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

188

282

376

470

<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:

0.0390

AC:

5706

AN:

146242

Hom.:

394

Cov.:

AF XY:

0.0373

AC XY:

2659

AN XY:

71212

show subpopulations

African (AFR)

AF:

0.134

AC:

5444

AN:

40714

American (AMR)

AF:

0.0126

AC:

186

AN:

14778

Ashkenazi Jewish (ASJ)

AF:

0.000885

AC:

AN:

3390

East Asian (EAS)

AF:

0.00

AC:

AN:

5026

South Asian (SAS)

AF:

0.000209

AC:

AN:

4790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8578

Middle Eastern (MID)

AF:

0.0138

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.000426

AC:

AN:

65756

Other (OTH)

AF:

0.0198

AC:

AN:

2022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

247

494

741

988

1235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0300

Hom.:

Bravo

AF:

0.0431

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Jun 06, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 26, 2017

Eurofins Ntd Llc (ga)

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.10

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.10

T;T

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.46

T;T

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-0.45

MutationAssessor

Benign

0.0

.;N

PhyloP100

1.8

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.67

N;N

REVEL

Uncertain

0.32

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.043

D;D

Polyphen

0.0020

.;B

Vest4

0.26

MutPred

0.22

Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);

ClinPred

0.058

GERP RS

1.1

PromoterAI

-0.070

Neutral

(source)

Varity_R

0.13

gMVP

0.14

Mutation Taster

=97/3

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over