chr8-132480521-C-T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_004519.4(KCNQ3):c.12G>A(p.Lys4Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000928 in 1,077,840 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 Likely benign (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 9.3e-7 ( 0 hom. )
Consequence
KCNQ3
NM_004519.4 synonymous
NM_004519.4 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 0.422
Publications
0 publications found
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]
KCNQ3 Gene-Disease associations (from GenCC):
- seizures, benign familial neonatal, 2Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
- benign familial infantile epilepsyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- benign neonatal seizuresInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- genetic developmental and epileptic encephalopathyInheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP6
Variant 8-132480521-C-T is Benign according to our data. Variant chr8-132480521-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 471216.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.422 with no splicing effect.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| KCNQ3 | ENST00000388996.10 | c.12G>A | p.Lys4Lys | synonymous_variant | Exon 1 of 15 | 1 | NM_004519.4 | ENSP00000373648.3 | ||
| KCNQ3 | ENST00000519445.5 | c.12G>A | p.Lys4Lys | synonymous_variant | Exon 1 of 15 | 5 | ENSP00000428790.1 | |||
| KCNQ3 | ENST00000519589.1 | n.-211G>A | upstream_gene_variant | 2 | ||||||
| KCNQ3 | ENST00000639358.1 | n.-214G>A | upstream_gene_variant | 5 | ENSP00000492691.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 9.28e-7 AC: 1AN: 1077840Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 528540 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1077840
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
528540
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
21646
American (AMR)
AF:
AC:
1
AN:
21138
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
14174
East Asian (EAS)
AF:
AC:
0
AN:
11408
South Asian (SAS)
AF:
AC:
0
AN:
49602
European-Finnish (FIN)
AF:
AC:
0
AN:
16772
Middle Eastern (MID)
AF:
AC:
0
AN:
3148
European-Non Finnish (NFE)
AF:
AC:
0
AN:
900900
Other (OTH)
AF:
AC:
0
AN:
39052
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Benign neonatal seizures Benign:1
Jun 01, 2017
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Uncertain
PhyloP100
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
Publications
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