rs6714959

Variant names:

• chr2-17930227-T-G
• rs6714959
• NM_002252.5:c.-59-723T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002252.5(KCNS3):​c.-59-723T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0495 in 152,168 control chromosomes in the GnomAD database, including 498 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.049 (498 hom., cov: 32)
• Consequence: KCNS3 NM_002252.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.586
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNS3	NM_002252.5	c.-59-723T>G		intron_variant	Intron 2 of 2	ENST00000304101.9	NP_002243.3
KCNS3	NM_001282428.2	c.-59-723T>G		intron_variant	Intron 2 of 2		NP_001269357.1
KCNS3	XM_011532825.2	c.-60+570T>G		intron_variant	Intron 3 of 3		XP_011531127.1
KCNS3	XM_047444255.1	c.-59-723T>G		intron_variant	Intron 2 of 2		XP_047300211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNS3	ENST00000304101.9	c.-59-723T>G		intron_variant	Intron 2 of 2	1	NM_002252.5	ENSP00000305824.4
KCNS3	ENST00000403915.5	c.-59-723T>G		intron_variant	Intron 2 of 2	1		ENSP00000385968.1
KCNS3	ENST00000419802.1	c.-59-723T>G		intron_variant	Intron 2 of 2	3		ENSP00000400098.1
KCNS3	ENST00000465292.5	n.305+12356T>G		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.0492 AC: 7486 AN: 152050 Hom.: 493 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0311

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0303

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00465

Gnomad OTH AF: 0.0526

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0495 AC: 7528 AN: 152168 Hom.: 498 Cov.: 32 AF XY: 0.0487 AC XY: 3624 AN XY: 74404

African (AFR) AF: 0.153 AC: 6343 AN: 41488

American (AMR) AF: 0.0311 AC: 475 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 118 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.0305 AC: 147 AN: 4816

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10606

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.00465 AC: 316 AN: 68006

Other (OTH) AF: 0.0520 AC: 110 AN: 2114

Alfa AF: 0.0371 Hom.: 48

Bravo AF: 0.0570

Asia WGS AF: 0.0190 AC: 68 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	17
DANN	Benign	0.66
PhyloP100		0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6714959; hg19: chr2-18111494;