19-50320323-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_004977.3(KCNC3):c.2197C>A(p.Gln733Lys) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 17)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

KCNC3
NM_004977.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.76

Publications

1 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.116850734).

BP6

Variant 19-50320323-G-T is Benign according to our data. Variant chr19-50320323-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3287524.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000238 (31/130222) while in subpopulation NFE AF = 0.000363 (22/60688). AF 95% confidence interval is 0.000244. There are 0 homozygotes in GnomAd4. There are 17 alleles in the male GnomAd4 subpopulation. Median coverage is 17. This position passed quality control check.

BS2

High AC in GnomAd4 at 31 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNC3	NM_004977.3 link	c.2197C>A	p.Gln733Lys	missense_variant	Exon 4 of 5	ENST00000477616.2	NP_004968.2	Q14003
KCNC3	NM_001372305.1 link	c.1969C>A	p.Gln657Lys	missense_variant	Exon 4 of 5		NP_001359234.1
KCNC3	NR_110912.2 link	n.260+270C>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNC3	ENST00000477616.2 link	c.2197C>A	p.Gln733Lys	missense_variant	Exon 4 of 5	1	NM_004977.3	ENSP00000434241.1	Q14003
KCNC3	ENST00000670667.1 link	c.2170+270C>A		intron_variant	Intron 3 of 3			ENSP00000499301.1	A0A590UJ62
KCNC3	ENST00000376959.6 link	c.2170+270C>A		intron_variant	Intron 3 of 4	5		ENSP00000366158.2	E7ETH1
KCNC3	ENST00000474951.1 link	c.118+270C>A		intron_variant	Intron 2 of 3	2		ENSP00000432438.1	E9PQY4

Frequencies

GnomAD3 genomes

AF:

0.000238

AC:

AN:

130110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00345

Gnomad NFE

AF:

0.000362

Gnomad OTH

AF:

0.000559

GnomAD2 exomes

AF:

0.0000553

AC:

AN:

54204

AF XY:

0.0000363

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000108

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000978

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000168

AC:

AN:

346114

Hom.:

Cov.:

AF XY:

0.000158

AC XY:

AN XY:

177572

show subpopulations

African (AFR)

AF:

0.000207

AC:

AN:

9640

American (AMR)

AF:

0.00

AC:

AN:

12974

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8230

East Asian (EAS)

AF:

0.00

AC:

AN:

15446

South Asian (SAS)

AF:

0.00

AC:

AN:

37836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17042

Middle Eastern (MID)

AF:

0.000584

AC:

AN:

1712

European-Non Finnish (NFE)

AF:

0.000226

AC:

AN:

225908

Other (OTH)

AF:

0.000231

AC:

AN:

17326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000238

AC:

AN:

130222

Hom.:

Cov.:

AF XY:

0.000272

AC XY:

AN XY:

62412

show subpopulations

African (AFR)

AF:

0.000200

AC:

AN:

35072

American (AMR)

AF:

0.00

AC:

AN:

13300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3176

East Asian (EAS)

AF:

0.00

AC:

AN:

3612

South Asian (SAS)

AF:

0.00

AC:

AN:

3370

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8150

Middle Eastern (MID)

AF:

0.00373

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.000363

AC:

AN:

60688

Other (OTH)

AF:

0.000554

AC:

AN:

1806

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000279

Hom.:

ExAC

AF:

0.0000159

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

May 08, 2024

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.085

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.47

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.34

M_CAP

Pathogenic

0.32

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.30

MutationAssessor

Benign

0.0

PhyloP100

3.8

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

0.21

REVEL

Uncertain

0.34

Sift

Benign

0.29

Sift4G

Benign

0.45

Polyphen

0.0010

Vest4

0.13

MVP

0.72

ClinPred

0.057

GERP RS

2.3

Varity_R

0.063

gMVP

0.22

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

19-50320323-G-T

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