rs4240213

Variant names:

• chr2-17931206-G-A
• rs4240213
• NM_002252.5:c.198G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-17931206-G-A
• chr2-17931206-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002252.5(KCNS3):​c.198G>A​(p.Glu66Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.965 in 1,614,112 control chromosomes in the GnomAD database, including 752,402 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 0.94 (66948 hom., cov: 32)
  • Exomes 𝑓: 0.97 (685454 hom.)
• Consequence: KCNS3 NM_002252.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45
• Publications: 19 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=2.45 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.198G>A	p.Glu66Glu	synonymous	Exon 3 of 3	NP_002243.3
	KCNS3	NM_001282428.2		c.198G>A	p.Glu66Glu	synonymous	Exon 3 of 3	NP_001269357.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNS3	ENST00000304101.9	TSL:1 MANE Select	c.198G>A	p.Glu66Glu	synonymous	Exon 3 of 3	ENSP00000305824.4
	KCNS3	ENST00000403915.5	TSL:1	c.198G>A	p.Glu66Glu	synonymous	Exon 3 of 3	ENSP00000385968.1
	KCNS3	ENST00000419802.1	TSL:3	c.198G>A	p.Glu66Glu	synonymous	Exon 3 of 3	ENSP00000400098.1

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142359 AN: 152114 Hom.: 66894 Cov.: 32

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.968

Gnomad AMR AF: 0.966

Gnomad ASJ AF: 0.957

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.989

Gnomad FIN AF: 0.979

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.938

GnomAD2 exomes AF: 0.966 AC: 243010 AN: 251476 AF XY: 0.969

Gnomad AFR exome AF: 0.840

Gnomad AMR exome AF: 0.980

Gnomad ASJ exome AF: 0.954

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.979

Gnomad NFE exome AF: 0.968

Gnomad OTH exome AF: 0.967

GnomAD4 exome AF: 0.968 AC: 1415260 AN: 1461880 Hom.: 685454 Cov.: 63 AF XY: 0.969 AC XY: 704776 AN XY: 727246

African (AFR) AF: 0.835 AC: 27947 AN: 33480

American (AMR) AF: 0.978 AC: 43757 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.954 AC: 24940 AN: 26136

East Asian (EAS) AF: 1.00 AC: 39698 AN: 39700

South Asian (SAS) AF: 0.987 AC: 85123 AN: 86258

European-Finnish (FIN) AF: 0.978 AC: 52228 AN: 53420

Middle Eastern (MID) AF: 0.969 AC: 5592 AN: 5768

European-Non Finnish (NFE) AF: 0.969 AC: 1077951 AN: 1111998

Other (OTH) AF: 0.961 AC: 58024 AN: 60396

GnomAD4 genome AF: 0.936 AC: 142471 AN: 152232 Hom.: 66948 Cov.: 32 AF XY: 0.939 AC XY: 69888 AN XY: 74450

African (AFR) AF: 0.842 AC: 34960 AN: 41502

American (AMR) AF: 0.966 AC: 14782 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.957 AC: 3321 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5182

South Asian (SAS) AF: 0.989 AC: 4761 AN: 4814

European-Finnish (FIN) AF: 0.979 AC: 10386 AN: 10614

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.969 AC: 65929 AN: 68036

Other (OTH) AF: 0.938 AC: 1978 AN: 2108

Alfa AF: 0.956 Hom.: 112142

Bravo AF: 0.930

Asia WGS AF: 0.987 AC: 3433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	4.6
DANN	Benign	0.46
PhyloP100		2.5
Mutation Taster		=97/3	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: rs4240213; hg19: chr2-18112473; COSMIC: COSV108156508;