chr2-17931388-A-G

Variant names:

• chr2-17931388-A-G
• rs1662961721
• NM_002252.5:c.380A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002252.5(KCNS3):​c.380A>G​(p.Glu127Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCNS3 NM_002252.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.18
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12874454).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNS3	NM_002252.5	MANE Select	c.380A>G	p.Glu127Gly	missense	Exon 3 of 3	NP_002243.3
	KCNS3	NM_001282428.2		c.380A>G	p.Glu127Gly	missense	Exon 3 of 3	NP_001269357.1	Q9BQ31

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNS3	ENST00000304101.9	TSL:1 MANE Select	c.380A>G	p.Glu127Gly	missense	Exon 3 of 3	ENSP00000305824.4	Q9BQ31
	KCNS3	ENST00000403915.5	TSL:1	c.380A>G	p.Glu127Gly	missense	Exon 3 of 3	ENSP00000385968.1	Q9BQ31
	KCNS3	ENST00000869571.1		c.380A>G	p.Glu127Gly	missense	Exon 2 of 2	ENSP00000539630.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		7.2
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.13
Sift	Benign	0.25	T
Sift4G	Benign	0.18	T
Polyphen		0.016	B
Vest4		0.27
MutPred		0.45		Loss of stability (P = 0.0322)
MVP		0.73
MPC		0.40
ClinPred		0.81	D
GERP RS		5.7
Varity_R		0.096
gMVP		0.36
Mutation Taster		=83/17	polymorphism

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: rs1662961721; hg19: chr2-18112655;