chr2-17932153-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_002252.5(KCNS3):c.1145C>T(p.Ala382Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,613,920 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0058 ( 5 hom., cov: 32)
Exomes 𝑓: 0.00075 ( 13 hom. )
Consequence
KCNS3
NM_002252.5 missense
NM_002252.5 missense
Scores
1
16
Clinical Significance
Conservation
PhyloP100: 0.665
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.012160063).
BP6
?
Variant 2-17932153-C-T is Benign according to our data. Variant chr2-17932153-C-T is described in ClinVar as [Benign]. Clinvar id is 789964.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0058 (882/152074) while in subpopulation AFR AF= 0.0187 (777/41468). AF 95% confidence interval is 0.0176. There are 5 homozygotes in gnomad4. There are 422 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KCNS3 | NM_002252.5 | c.1145C>T | p.Ala382Val | missense_variant | 3/3 | ENST00000304101.9 | |
KCNS3 | NM_001282428.2 | c.1145C>T | p.Ala382Val | missense_variant | 3/3 | ||
KCNS3 | XM_011532825.2 | c.1145C>T | p.Ala382Val | missense_variant | 4/4 | ||
KCNS3 | XM_047444255.1 | c.1145C>T | p.Ala382Val | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KCNS3 | ENST00000304101.9 | c.1145C>T | p.Ala382Val | missense_variant | 3/3 | 1 | NM_002252.5 | P1 | |
KCNS3 | ENST00000403915.5 | c.1145C>T | p.Ala382Val | missense_variant | 3/3 | 1 | P1 | ||
KCNS3 | ENST00000465292.5 | n.305+14282C>T | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00575 AC: 874AN: 151956Hom.: 5 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00176 AC: 443AN: 251224Hom.: 4 AF XY: 0.00143 AC XY: 194AN XY: 135762
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GnomAD4 exome AF: 0.000750 AC: 1096AN: 1461846Hom.: 13 Cov.: 41 AF XY: 0.000675 AC XY: 491AN XY: 727218
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GnomAD4 genome ? AF: 0.00580 AC: 882AN: 152074Hom.: 5 Cov.: 32 AF XY: 0.00568 AC XY: 422AN XY: 74344
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Mar 29, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at