NM_002252.5:c.359G>T

Variant names:

• chr2-17931367-G-T
• rs147647932
• NM_002252.5:c.359G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002252.5(KCNS3):​c.359G>T​(p.Arg120Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCNS3 NM_002252.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.76

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNS3	NM_002252.5	c.359G>T	p.Arg120Leu	missense_variant	Exon 3 of 3	ENST00000304101.9	NP_002243.3
KCNS3	NM_001282428.2	c.359G>T	p.Arg120Leu	missense_variant	Exon 3 of 3		NP_001269357.1
KCNS3	XM_011532825.2	c.359G>T	p.Arg120Leu	missense_variant	Exon 4 of 4		XP_011531127.1
KCNS3	XM_047444255.1	c.359G>T	p.Arg120Leu	missense_variant	Exon 3 of 3		XP_047300211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNS3	ENST00000304101.9	c.359G>T	p.Arg120Leu	missense_variant	Exon 3 of 3	1	NM_002252.5	ENSP00000305824.4
KCNS3	ENST00000403915.5	c.359G>T	p.Arg120Leu	missense_variant	Exon 3 of 3	1		ENSP00000385968.1
KCNS3	ENST00000465292.5	n.305+13496G>T		intron_variant	Intron 2 of 4	4
KCNS3	ENST00000419802.1	c.*136G>T		downstream_gene_variant		3		ENSP00000400098.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.78	.;T
M_CAP	Benign	0.0077	T
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-5.1	D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0050	D;D
Sift4G	Benign	0.30	T;T
Polyphen		0.65	P;P
Vest4		0.64
MutPred		0.41		Loss of disorder (P = 0.0559);Loss of disorder (P = 0.0559);
MVP		0.62
MPC		0.64
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.36
gMVP		0.57

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: rs147647932; hg19: chr2-18112634;