rs111744086

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004977.3(KCNC3):c.1929C>T(p.Gly643Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,545,834 control chromosomes in the GnomAD database, including 131 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 26 hom., cov: 32)

Exomes 𝑓: 0.010 ( 105 hom. )

Consequence

KCNC3
NM_004977.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.84

Publications

0 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 19-50323024-G-A is Benign according to our data. Variant chr19-50323024-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 288184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.84 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0142 (2155/152246) while in subpopulation AFR AF = 0.0236 (979/41564). AF 95% confidence interval is 0.0223. There are 26 homozygotes in GnomAd4. There are 1013 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2155 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
KCNC3	NM_004977.3 link	c.1929C>T	p.Gly643Gly	synonymous_variant	Exon 2 of 5	ENST00000477616.2	NP_004968.2
KCNC3	NM_001372305.1 link	c.1701C>T	p.Gly567Gly	synonymous_variant	Exon 2 of 5		NP_001359234.1
KCNC3	NR_110912.2 link	n.69-2240C>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
KCNC3	ENST00000477616.2 link	c.1929C>T	p.Gly643Gly	synonymous_variant	Exon 2 of 5	1	NM_004977.3	ENSP00000434241.1
KCNC3	ENST00000670667.1 link	c.1929C>T	p.Gly643Gly	synonymous_variant	Exon 2 of 4			ENSP00000499301.1
KCNC3	ENST00000376959.6 link	c.1929C>T	p.Gly643Gly	synonymous_variant	Exon 2 of 5	5		ENSP00000366158.2
KCNC3	ENST00000474951.1 link	c.-74-2240C>T		intron_variant	Intron 1 of 3	2		ENSP00000432438.1

Frequencies

GnomAD3 genomes

AF:

0.0141

AC:

2150

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0235

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0177

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.00566

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0113

Gnomad OTH

AF:

0.0158

GnomAD2 exomes

AF:

0.00953

AC:

1358

AN:

142518

AF XY:

0.00937

show subpopulations

Gnomad AFR exome

AF:

0.0229

Gnomad AMR exome

AF:

0.0113

Gnomad ASJ exome

AF:

0.00838

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00860

Gnomad NFE exome

AF:

0.0117

Gnomad OTH exome

AF:

0.0108

GnomAD4 exome

AF:

0.0105

AC:

14593

AN:

1393588

Hom.:

105

Cov.:

AF XY:

0.0102

AC XY:

7002

AN XY:

687196

show subpopulations

African (AFR)

AF:

0.0230

AC:

725

AN:

31520

American (AMR)

AF:

0.0108

AC:

383

AN:

35326

Ashkenazi Jewish (ASJ)

AF:

0.00843

AC:

210

AN:

24922

East Asian (EAS)

AF:

0.0000560

AC:

AN:

35738

South Asian (SAS)

AF:

0.00313

AC:

246

AN:

78628

European-Finnish (FIN)

AF:

0.00806

AC:

384

AN:

47626

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

4700

European-Non Finnish (NFE)

AF:

0.0111

AC:

11966

AN:

1077412

Other (OTH)

AF:

0.0109

AC:

629

AN:

57716

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

721

1441

2162

2882

3603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

454

908

1362

1816

2270

<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:

0.0142

AC:

2155

AN:

152246

Hom.:

Cov.:

AF XY:

0.0136

AC XY:

1013

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0236

AC:

979

AN:

41564

American (AMR)

AF:

0.0177

AC:

271

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00519

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00566

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0113

AC:

771

AN:

68004

Other (OTH)

AF:

0.0156

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

111

221

332

442

553

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0123

Hom.:

Bravo

AF:

0.0155

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 04, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 07, 2017

Athena Diagnostics

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

- -

Spinocerebellar ataxia type 13

Benign:2

Oct 10, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jun 16, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.6

(source)

DANN

Benign

0.84

PhyloP100

-2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism

(source)

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

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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