2-17931439-C-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000304101.9(KCNS3):āc.431C>Gā(p.Ser144Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,614,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00022 ( 0 hom., cov: 32)
Exomes š: 0.000016 ( 0 hom. )
Consequence
KCNS3
ENST00000304101.9 missense
ENST00000304101.9 missense
Scores
1
9
9
Clinical Significance
Conservation
PhyloP100: 7.91
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13271233).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KCNS3 | NM_002252.5 | c.431C>G | p.Ser144Cys | missense_variant | 3/3 | ENST00000304101.9 | NP_002243.3 | |
KCNS3 | NM_001282428.2 | c.431C>G | p.Ser144Cys | missense_variant | 3/3 | NP_001269357.1 | ||
KCNS3 | XM_011532825.2 | c.431C>G | p.Ser144Cys | missense_variant | 4/4 | XP_011531127.1 | ||
KCNS3 | XM_047444255.1 | c.431C>G | p.Ser144Cys | missense_variant | 3/3 | XP_047300211.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KCNS3 | ENST00000304101.9 | c.431C>G | p.Ser144Cys | missense_variant | 3/3 | 1 | NM_002252.5 | ENSP00000305824 | P1 | |
KCNS3 | ENST00000403915.5 | c.431C>G | p.Ser144Cys | missense_variant | 3/3 | 1 | ENSP00000385968 | P1 | ||
KCNS3 | ENST00000465292.5 | n.305+13568C>G | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.000217 AC: 33AN: 152172Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
33
AN:
152172
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251110Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135702
GnomAD3 exomes
AF:
AC:
9
AN:
251110
Hom.:
AF XY:
AC XY:
4
AN XY:
135702
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461878Hom.: 0 Cov.: 42 AF XY: 0.0000151 AC XY: 11AN XY: 727242
GnomAD4 exome
AF:
AC:
24
AN:
1461878
Hom.:
Cov.:
42
AF XY:
AC XY:
11
AN XY:
727242
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000217 AC: 33AN: 152172Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74330
GnomAD4 genome
AF:
AC:
33
AN:
152172
Hom.:
Cov.:
32
AF XY:
AC XY:
16
AN XY:
74330
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
9
ESP6500EA
AF:
AC:
0
ExAC
AF:
AC:
6
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 18, 2023 | The c.431C>G (p.S144C) alteration is located in exon 3 (coding exon 1) of the KCNS3 gene. This alteration results from a C to G substitution at nucleotide position 431, causing the serine (S) at amino acid position 144 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Uncertain
D;D
Polyphen
P;P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at