2-18092493-T-C

Position:

• chr2-18092493-T-C

Variant summary

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

The ENST00000465292.5(KCNS3):​n.306-77897T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,120 control chromosomes in the GnomAD database, including 6,285 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 0.25 (6285 hom., cov: 32)
• Consequence: KCNS3 ENST00000465292.5 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNS3	ENST00000465292.5	n.306-77897T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37457 AN: 152002 Hom.: 6266 Cov.: 32

Gnomad AFR AF: 0.476

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.0888

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.247 AC: 37527 AN: 152120 Hom.: 6285 Cov.: 32 AF XY: 0.246 AC XY: 18272 AN XY: 74392

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.0888

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.201

Alfa AF: 0.0753 Hom.: 97

Bravo AF: 0.260

Asia WGS AF: 0.281 AC: 977 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2345101; hg19: chr2-18273759;