rs10177831

Positions:

• chr2-17899115-G-A

Variant summary

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

The NM_002252.5(KCNS3):​c.-251-18565G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,696 control chromosomes in the GnomAD database, including 18,960 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 0.49 (18960 hom., cov: 30)
• Consequence: KCNS3 NM_002252.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830

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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNS3	NM_002252.5	c.-251-18565G>A		intron_variant		ENST00000304101.9
KCNS3	NM_001282428.2	c.-251-18565G>A		intron_variant
KCNS3	XM_011532825.2	c.-622-18565G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNS3	ENST00000304101.9	c.-251-18565G>A		intron_variant		1	NM_002252.5	P1

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74753 AN: 151578 Hom.: 18956 Cov.: 30

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.493 AC: 74775 AN: 151696 Hom.: 18960 Cov.: 30 AF XY: 0.486 AC XY: 36004 AN XY: 74118

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.434

Gnomad4 ASJ AF: 0.568

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.366

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.489

Alfa AF: 0.527 Hom.: 2665

Bravo AF: 0.487

Asia WGS AF: 0.369 AC: 1285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.79
DANN	Benign	0.42

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: rs10177831; hg19: chr2-18080382;