rs758790946

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004519.4(KCNQ3):​c.2072G>T​(p.Gly691Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,614,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

KCNQ3
NM_004519.4 missense

Scores

8
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.57
Variant links:
Genes affected
KCNQ3 (HGNC:6297): (potassium voltage-gated channel subfamily Q member 3) This gene encodes a protein that functions in the regulation of neuronal excitability. The encoded protein forms an M-channel by associating with the products of the related KCNQ2 or KCNQ5 genes, which both encode integral membrane proteins. M-channel currents are inhibited by M1 muscarinic acetylcholine receptors and are activated by retigabine, a novel anti-convulsant drug. Defects in this gene are a cause of benign familial neonatal convulsions type 2 (BFNC2), also known as epilepsy, benign neonatal type 2 (EBN2). Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.21994334).
BS2
High AC in GnomAdExome4 at 43 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KCNQ3NM_004519.4 linkc.2072G>T p.Gly691Val missense_variant 15/15 ENST00000388996.10 NP_004510.1 O43525-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KCNQ3ENST00000388996.10 linkc.2072G>T p.Gly691Val missense_variant 15/151 NM_004519.4 ENSP00000373648.3 O43525-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152128
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251460
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000294
AC:
43
AN:
1461890
Hom.:
0
Cov.:
32
AF XY:
0.0000275
AC XY:
20
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000378
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152128
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Uncertain
0.085
D
BayesDel_noAF
Uncertain
-0.050
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.47
T;.;.;.;.
Eigen
Benign
-0.21
Eigen_PC
Benign
0.0016
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.84
T;T;T;T;T
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.22
T;T;T;T;T
MetaSVM
Uncertain
0.69
D
MutationAssessor
Benign
0.69
N;.;.;.;.
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-1.8
N;.;N;N;.
REVEL
Uncertain
0.45
Sift
Benign
0.031
D;.;D;D;.
Sift4G
Benign
0.13
T;T;T;T;.
Polyphen
0.22
B;.;.;B;.
Vest4
0.14
MutPred
0.32
Loss of disorder (P = 0.0707);.;.;.;.;
MVP
0.49
MPC
0.14
ClinPred
0.17
T
GERP RS
5.5
Varity_R
0.17
gMVP
0.34

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs758790946; hg19: chr8-133142056; API