Variant 10-77637586-TCCGCCGCCGCCGCCG-TCCGCCGCCGCCG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting

The NM_001161352.2(KCNMA1):c.54_56del(p.Gly20del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000317 in 1,515,216 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G18G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000093 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

KCNMA1
NM_001161352.2 inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.59

Variant links:

Genes affected

KCNMA1 (HGNC:6284): (potassium calcium-activated channel subfamily M alpha 1) This gene encodes the alpha subunit of calcium-activated BK channel. The encoded protein is involved in several physiological processes including smooth muscle contraction, neurotransmitter release and neuronal excitability. Mutations in this gene are associated with a spectrum of neurological disorders including Paroxysmal Nonkinesigenic Dyskinesia 3, Idiopathic Generalized Epilepsy 16 and Liang-Wang syndrome. [provided by RefSeq, Aug 2022]

KCNMA1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000342 (466/1364006) while in subpopulation AMR AF= 0.000905 (31/34256). AF 95% confidence interval is 0.000655. There are 0 homozygotes in gnomad4_exome. There are 233 alleles in male gnomad4_exome subpopulation. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNMA1	NM_001161352.2 linkuse as main transcript	c.54_56del	p.Gly20del	inframe_deletion	1/28	ENST00000286628.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNMA1	ENST00000286628.14 linkuse as main transcript	c.54_56del	p.Gly20del	inframe_deletion	1/28	1	NM_001161352.2	A2	Q12791-1

Frequencies

GnomAD3 genomes

AF:

0.0000927

AC:

AN:

151106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

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:

0.0000887

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00146

AC:

167

AN:

114424

Hom.:

AF XY:

0.00148

AC XY:

AN XY:

62920

show subpopulations

Gnomad AFR exome

AF:

0.00249

Gnomad AMR exome

AF:

0.00115

Gnomad ASJ exome

AF:

0.00181

Gnomad EAS exome

AF:

0.00117

Gnomad SAS exome

AF:

0.00158

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.00146

Gnomad OTH exome

AF:

0.000873

GnomAD4 exome

AF:

0.000342

AC:

466

AN:

1364006

Hom.:

AF XY:

0.000346

AC XY:

233

AN XY:

672650

show subpopulations

Gnomad4 AFR exome

AF:

0.000620

Gnomad4 AMR exome

AF:

0.000905

Gnomad4 ASJ exome

AF:

0.000653

Gnomad4 EAS exome

AF:

0.000315

Gnomad4 SAS exome

AF:

0.000519

Gnomad4 FIN exome

AF:

0.000410

Gnomad4 NFE exome

AF:

0.000297

Gnomad4 OTH exome

AF:

0.000281

GnomAD4 genome

AF:

0.0000926

AC:

AN:

151210

Hom.:

Cov.:

AF XY:

0.0000541

AC XY:

AN XY:

73876

show subpopulations

Gnomad4 AFR

AF:

0.000170

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000887

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Generalized epilepsy-paroxysmal dyskinesia syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Jan 11, 2024

This variant, c.54_56del, results in the deletion of 1 amino acid(s) of the KCNMA1 protein (p.Gly20del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with KCNMA1-related conditions. 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

Name

Calibrated prediction

Score

Prediction

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over