2-17932153-C-T

Position:

chr2-17932153-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000304101.9(KCNS3):c.1145C>T(p.Ala382Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,613,920 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00075 ( 13 hom. )

Consequence

KCNS3
ENST00000304101.9 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.665

Variant links:

Genes affected

KCNS3 (HGNC:6302): (potassium voltage-gated channel modifier subfamily S member 3) Voltage-gated potassium channels form the largest and most diversified class of ion channels and are present in both excitable and nonexcitable cells. Their main functions are associated with the regulation of the resting membrane potential and the control of the shape and frequency of action potentials. The alpha subunits are of 2 types: those that are functional by themselves and those that are electrically silent but capable of modulating the activity of specific functional alpha subunits. The protein encoded by this gene is not functional by itself but can form heteromultimers with member 1 and with member 2 (and possibly other members) of the Shab-related subfamily of potassium voltage-gated channel proteins. This gene belongs to the S subfamily of the potassium channel family. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Sep 2013]

KCNS3 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=0.012160063).

BP6

Variant 2-17932153-C-T is Benign according to our data. Variant chr2-17932153-C-T is described in ClinVar as [Benign]. Clinvar id is 789964.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0058 (882/152074) while in subpopulation AFR AF= 0.0187 (777/41468). AF 95% confidence interval is 0.0176. There are 5 homozygotes in gnomad4. There are 422 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KCNS3	NM_002252.5 linkuse as main transcript	c.1145C>T	p.Ala382Val	missense_variant	3/3	ENST00000304101.9	NP_002243.3
KCNS3	NM_001282428.2 linkuse as main transcript	c.1145C>T	p.Ala382Val	missense_variant	3/3		NP_001269357.1
KCNS3	XM_011532825.2 linkuse as main transcript	c.1145C>T	p.Ala382Val	missense_variant	4/4		XP_011531127.1
KCNS3	XM_047444255.1 linkuse as main transcript	c.1145C>T	p.Ala382Val	missense_variant	3/3		XP_047300211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KCNS3	ENST00000304101.9 linkuse as main transcript	c.1145C>T	p.Ala382Val	missense_variant	3/3	1	NM_002252.5	ENSP00000305824	P1
KCNS3	ENST00000403915.5 linkuse as main transcript	c.1145C>T	p.Ala382Val	missense_variant	3/3	1		ENSP00000385968	P1
KCNS3	ENST00000465292.5 linkuse as main transcript	n.305+14282C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00575

AC:

874

AN:

151956

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00485

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00623

GnomAD3 exomes

AF:

0.00176

AC:

443

AN:

251224

Hom.:

AF XY:

0.00143

AC XY:

194

AN XY:

135762

show subpopulations

Gnomad AFR exome

AF:

0.0188

Gnomad AMR exome

AF:

0.00223

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000379

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.000750

AC:

1096

AN:

1461846

Hom.:

Cov.:

AF XY:

0.000675

AC XY:

491

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0184

Gnomad4 AMR exome

AF:

0.00279

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000185

Gnomad4 OTH exome

AF:

0.00189

GnomAD4 genome

AF:

0.00580

AC:

882

AN:

152074

Hom.:

Cov.:

AF XY:

0.00568

AC XY:

422

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0187

Gnomad4 AMR

AF:

0.00484

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.00725

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0229

AC:

101

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00187

AC:

227

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000533

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.27

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.096

LIST_S2

Benign

0.80

.;T

MetaRNN

Benign

0.012

T;T

MetaSVM

Uncertain

0.044

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.020

N;N

REVEL

Benign

0.28

Sift

Benign

0.26

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;B

Vest4

0.061

MVP

0.89

MPC

0.33

ClinPred

0.0016

GERP RS

-0.094

Varity_R

0.020

gMVP

0.75

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

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