rs10177831

Variant names:

• chr2-17899115-G-A
• rs10177831
• NM_002252.5:c.-251-18565G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002252.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNS3	NM_002252.5	MANE Select	c.-251-18565G>A		intron	N/A	NP_002243.3
	KCNS3	NM_001282428.2		c.-251-18565G>A		intron	N/A	NP_001269357.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNS3	ENST00000304101.9	TSL:1 MANE Select	c.-251-18565G>A		intron	N/A	ENSP00000305824.4
	KCNS3	ENST00000403915.5	TSL:1	c.-251-18565G>A		intron	N/A	ENSP00000385968.1
	KCNS3	ENST00000419802.1	TSL:3	c.-251-18565G>A		intron	N/A	ENSP00000400098.1

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

African (AFR) AF: 0.417 AC: 17266 AN: 41362

American (AMR) AF: 0.434 AC: 6611 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1968 AN: 3464

East Asian (EAS) AF: 0.397 AC: 2040 AN: 5136

South Asian (SAS) AF: 0.366 AC: 1758 AN: 4800

European-Finnish (FIN) AF: 0.451 AC: 4743 AN: 10520

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38669 AN: 67864

Other (OTH) AF: 0.489 AC: 1030 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.79
DANN	Benign	0.42
PhyloP100		-0.83
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: rs10177831; hg19: chr2-18080382;