8-132480483-TCGCCGCCGC-TCGC

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3

The NM_004519.4(KCNQ3):c.44_49delGCGGCG(p.Gly15_Gly16del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000282 in 1,063,240 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

KCNQ3
NM_004519.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.858

Publications

0 publications found

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]

KCNQ3 Gene-Disease associations (from GenCC):

seizures, benign familial neonatal, 2
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
benign familial infantile epilepsy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
benign neonatal seizures
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
genetic developmental and epileptic encephalopathy
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

KCNQ3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP3

Nonframeshift variant in repetitive region in NM_004519.4

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ3	NM_004519.4 link	c.44_49delGCGGCG	p.Gly15_Gly16del	disruptive_inframe_deletion	Exon 1 of 15	ENST00000388996.10	NP_004510.1	O43525-1
KCNQ3	XM_047421769.1 link	c.44_49delGCGGCG	p.Gly15_Gly16del	disruptive_inframe_deletion	Exon 1 of 15		XP_047277725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KCNQ3	ENST00000388996.10 link	c.44_49delGCGGCG	p.Gly15_Gly16del	disruptive_inframe_deletion	Exon 1 of 15	1	NM_004519.4	ENSP00000373648.3	O43525-1
KCNQ3	ENST00000519445.5 link	c.44_49delGCGGCG	p.Gly15_Gly16del	disruptive_inframe_deletion	Exon 1 of 15	5		ENSP00000428790.1	E7ET42
KCNQ3	ENST00000519589.1 link	n.-179_-174delGCGGCG		upstream_gene_variant		2
KCNQ3	ENST00000639358.1 link	n.-182_-177delGCGGCG		upstream_gene_variant		5		ENSP00000492691.1	A0A1W2PRN8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000282

AC:

AN:

1063240

Hom.:

AF XY:

0.00000197

AC XY:

AN XY:

508208

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21516

American (AMR)

AF:

0.00

AC:

AN:

7442

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12476

East Asian (EAS)

AF:

0.00

AC:

AN:

23278

South Asian (SAS)

AF:

0.00

AC:

AN:

20818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20146

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2834

European-Non Finnish (NFE)

AF:

0.00000328

AC:

AN:

913268

Other (OTH)

AF:

0.00

AC:

AN:

41462

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Benign neonatal seizures

Uncertain:1

Jun 23, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with KCNQ3-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.44_49del, results in the deletion of 2 amino acid(s) of the KCNQ3 protein (p.Gly15_Gly16del), but otherwise preserves the integrity of the reading frame. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.86

Mutation Taster

=171/29

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over