2-17931609-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002252.5(KCNS3):c.601G>A(p.Ala201Thr) 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. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KCNS3 NM_002252.5 missense
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 6.96

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4012372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNS3	NM_002252.5	c.601G>A	p.Ala201Thr	missense_variant	3/3	ENST00000304101.9
KCNS3	NM_001282428.2	c.601G>A	p.Ala201Thr	missense_variant	3/3
KCNS3	XM_011532825.2	c.601G>A	p.Ala201Thr	missense_variant	4/4
KCNS3	XM_047444255.1	c.601G>A	p.Ala201Thr	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNS3	ENST00000304101.9	c.601G>A	p.Ala201Thr	missense_variant	3/3	1	NM_002252.5	P1
KCNS3	ENST00000403915.5	c.601G>A	p.Ala201Thr	missense_variant	3/3	1		P1
KCNS3	ENST00000465292.5	n.305+13738G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 42

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Autism spectrum disorder Other:1

association, no assertion criteria provided

research

University of Washington Center for Mendelian Genomics, University of Washington

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.66	D;D
Eigen	Benign	0.042
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.40	T;T
MetaSVM	Uncertain	0.39	D
MutationAssessor	Benign	1.1	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Uncertain	0.41
Sift	Benign	0.27	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.0070	B;B
Vest4		0.39
MutPred		0.44		Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP		0.97
MPC		0.37
ClinPred		0.74	D
GERP RS		6.1
Varity_R		0.24
gMVP		0.46

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: rs1662975878; hg19: chr2-18112876;