rs10495680

Variant names:

• chr2-18172250-T-C
• rs10495680
• ENST00000465292.5:n.424+1742T>C

Variant summary

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

The ENST00000465292.5(KCNS3):​n.424+1742T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0432 in 152,246 control chromosomes in the GnomAD database, including 197 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 0.043 (197 hom., cov: 32)
• Consequence: KCNS3 ENST00000465292.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20

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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNS3	ENST00000465292.5	n.424+1742T>C		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes AF: 0.0431 AC: 6552 AN: 152128 Hom.: 195 Cov.: 32

Gnomad AFR AF: 0.0277

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0493

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0415

Gnomad OTH AF: 0.0421

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

GnomAD4 genome AF: 0.0432 AC: 6570 AN: 152246 Hom.: 197 Cov.: 32 AF XY: 0.0447 AC XY: 3326 AN XY: 74448

Gnomad4 AFR AF: 0.0278 AC: 0.0278273 AN: 0.0278273

Gnomad4 AMR AF: 0.0496 AC: 0.0495554 AN: 0.0495554

Gnomad4 ASJ AF: 0.0271 AC: 0.0270737 AN: 0.0270737

Gnomad4 EAS AF: 0.121 AC: 0.121329 AN: 0.121329

Gnomad4 SAS AF: 0.138 AC: 0.137795 AN: 0.137795

Gnomad4 FIN AF: 0.0311 AC: 0.031138 AN: 0.031138

Gnomad4 NFE AF: 0.0415 AC: 0.0414878 AN: 0.0414878

Gnomad4 OTH AF: 0.0408 AC: 0.0407583 AN: 0.0407583

Alfa AF: 0.0460 Hom.: 114

Bravo AF: 0.0420

Asia WGS AF: 0.114 AC: 399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10495680; hg19: chr2-18353516;