rs981093917

chr8-132480483-TCGCCGCCGC-Tchr8-132480483-TCGCCGCCGC-TCGCchr8-132480483-TCGCCGCCGC-TCGCCGCchr8-132480483-TCGCCGCCGC-TCGCCGCCGCCGCchr8-132480483-TCGCCGCCGC-TCGCCGCCGCCGCCGC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_004519.4(KCNQ3):c.41_49del(p.Gly14_Gly16del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000165 in 1,211,130 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G14G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000018 (1 hom.)
• Consequence: KCNQ3 NM_004519.4 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.896

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNQ3	NM_004519.4	c.41_49del	p.Gly14_Gly16del	inframe_deletion	1/15	ENST00000388996.10
KCNQ3	XM_047421769.1	c.41_49del	p.Gly14_Gly16del	inframe_deletion	1/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNQ3	ENST00000388996.10	c.41_49del	p.Gly14_Gly16del	inframe_deletion	1/15	1	NM_004519.4	P1
KCNQ3	ENST00000519445.5	c.41_49del	p.Gly14_Gly16del	inframe_deletion	1/15	5

Frequencies

GnomAD3 genomes AF: 0.00000676 AC: 1 AN: 147890 Hom.: 0 Cov.: 32

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: 0.000214

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000179 AC: 19 AN: 1063240 Hom.: 1 AF XY: 0.0000197 AC XY: 10 AN XY: 508208

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: 0.000576

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000657

Gnomad4 OTH exome AF: 0.0000241

GnomAD4 genome AF: 0.00000676 AC: 1 AN: 147890 Hom.: 0 Cov.: 32 AF XY: 0.0000139 AC XY: 1 AN XY: 72080

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000214

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Benign neonatal seizures Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Apr 20, 2022

This variant has not been reported in the literature in individuals affected with KCNQ3-related conditions. This variant, c.41_49del, results in the deletion of 3 amino acid(s) of the KCNQ3 protein (p.Gly14_Gly16del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs981093917; hg19: chr8-133492730;