10-77637586-TCCGCCGCCGCCGCCG-TCCG

Variant names:

• chr10-77637586-TCCGCCGCCGCCG-T
• rs760628050
• NM_001161352.2:c.45_56delCGGCGGCGGCGG

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001161352.2(KCNMA1):​c.45_56delCGGCGGCGGCGG​(p.Gly16_Gly19del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000146 in 1,373,658 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G15G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: KCNMA1 NM_001161352.2 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.59
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• generalized epilepsy-paroxysmal dyskinesia syndrome

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Illumina, G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
• Liang-Wang syndrome

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• cerebellar atrophy, developmental delay, and seizures

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001161352.2

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNMA1	NM_001161352.2	c.45_56delCGGCGGCGGCGG	p.Gly16_Gly19del	disruptive_inframe_deletion	Exon 1 of 28	ENST00000286628.14	NP_001154824.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNMA1	ENST00000286628.14	c.45_56delCGGCGGCGGCGG	p.Gly16_Gly19del	disruptive_inframe_deletion	Exon 1 of 28	1	NM_001161352.2	ENSP00000286628.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 114424 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1373658 Hom.: 0 AF XY: 0.00000295 AC XY: 2 AN XY: 677468

African (AFR) AF: 0.00 AC: 0 AN: 30918

American (AMR) AF: 0.00 AC: 0 AN: 34690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24708

East Asian (EAS) AF: 0.00 AC: 0 AN: 35200

South Asian (SAS) AF: 0.00 AC: 0 AN: 77968

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36758

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5006

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1071128

Other (OTH) AF: 0.00 AC: 0 AN: 57282

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.6

Splicing

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

Other links and lift over

dbSNP: rs760628050; hg19: chr10-79397344;