rs6714959

Positions:

• chr2-17930227-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
KCNS3	NM_002252.5	c.-59-723T>G		intron_variant		ENST00000304101.9	NP_002243.3
KCNS3	NM_001282428.2	c.-59-723T>G		intron_variant			NP_001269357.1
KCNS3	XM_011532825.2	c.-60+570T>G		intron_variant			XP_011531127.1
KCNS3	XM_047444255.1	c.-59-723T>G		intron_variant			XP_047300211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNS3	ENST00000304101.9	c.-59-723T>G		intron_variant		1	NM_002252.5	ENSP00000305824	P1
KCNS3	ENST00000403915.5	c.-59-723T>G		intron_variant		1		ENSP00000385968	P1
KCNS3	ENST00000419802.1	c.-59-723T>G		intron_variant		3		ENSP00000400098
KCNS3	ENST00000465292.5	n.305+12356T>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.0311

Gnomad4 ASJ AF: 0.0340

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0305

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00465

Gnomad4 OTH AF: 0.0520

Alfa AF: 0.0327 Hom.: 38

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

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

Other links and lift over

dbSNP: rs6714959; hg19: chr2-18111494;