2-17979049-C-T

Variant names:

• chr2-17979049-C-T
• rs10495674
• ENST00000465292.5:n.305+61178C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000465292.5(KCNS3):​n.305+61178C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0588 in 152,234 control chromosomes in the GnomAD database, including 658 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 0.059 (658 hom., cov: 32)
• Consequence: KCNS3 ENST00000465292.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.307 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.305+61178C>T		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.0587 AC: 8930 AN: 152118 Hom.: 652 Cov.: 32

Gnomad AFR AF: 0.0502

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.0519

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0180

Gnomad OTH AF: 0.0584

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

GnomAD4 genome AF: 0.0588 AC: 8951 AN: 152234 Hom.: 658 Cov.: 32 AF XY: 0.0665 AC XY: 4946 AN XY: 74428

Gnomad4 AFR AF: 0.0501

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.0357

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.0519

Gnomad4 NFE AF: 0.0180

Gnomad4 OTH AF: 0.0634

Alfa AF: 0.0377 Hom.: 141

Bravo AF: 0.0638

Asia WGS AF: 0.273 AC: 948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.88
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10495674; hg19: chr2-18160315;