rs750804948

Variant names:

• chr10-77637612-TGCCGCCGCCGCC-T
• rs750804948
• NM_001161352.2:c.19_30delGGCGGCGGCGGC

Your query was ambiguous. Multiple possible variants found:

• chr10-77637612-TGCCGCCGCCGCC-T
• chr10-77637612-TGCCGCCGCCGCC-TGCC
• chr10-77637612-TGCCGCCGCCGCC-TGCCGCC
• chr10-77637612-TGCCGCCGCCGCC-TGCCGCCGCC
• chr10-77637612-TGCCGCCGCCGCC-TGCCGCCGCCGCCGCC
• chr10-77637612-TGCCGCCGCCGCC-TGCCGCCGCCGCCGCCGCC
• chr10-77637612-TGCCGCCGCCGCC-TGCCGCCGCCGCCGCCGCCGCC
• chr10-77637612-TGCCGCCGCCGCC-TGCCGCCGCCGCCGCCGCCGCCGCC

Variant summary

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

The NM_001161352.2(KCNMA1):​c.19_30delGGCGGCGGCGGC​(p.Gly7_Gly10del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.00000526 in 1,521,096 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: KCNMA1 NM_001161352.2 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.76
• 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161352.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMA1	NM_001161352.2	MANE Select	c.19_30delGGCGGCGGCGGC	p.Gly7_Gly10del	conservative_inframe_deletion	Exon 1 of 28	NP_001154824.1
	KCNMA1	NM_001437422.1		c.19_30delGGCGGCGGCGGC	p.Gly7_Gly10del	conservative_inframe_deletion	Exon 1 of 28	NP_001424351.1
	KCNMA1	NM_001161353.2		c.19_30delGGCGGCGGCGGC	p.Gly7_Gly10del	conservative_inframe_deletion	Exon 1 of 28	NP_001154825.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMA1	ENST00000286628.14	TSL:1 MANE Select	c.19_30delGGCGGCGGCGGC	p.Gly7_Gly10del	conservative_inframe_deletion	Exon 1 of 28	ENSP00000286628.8
	KCNMA1	ENST00000626620.3	TSL:1	c.19_30delGGCGGCGGCGGC	p.Gly7_Gly10del	conservative_inframe_deletion	Exon 1 of 28	ENSP00000485867.1
	KCNMA1	ENST00000639406.1	TSL:1	c.19_30delGGCGGCGGCGGC	p.Gly7_Gly10del	conservative_inframe_deletion	Exon 1 of 29	ENSP00000491732.1

Frequencies

GnomAD3 genomes AF: 0.0000268 AC: 4 AN: 149320 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: 0.000808

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000253 AC: 3 AN: 118702 AF XY: 0.0000461

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000315

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000365 AC: 5 AN: 1371678 Hom.: 0 AF XY: 0.00000444 AC XY: 3 AN XY: 676312

African (AFR) AF: 0.00 AC: 0 AN: 30826

American (AMR) AF: 0.00 AC: 0 AN: 34540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24544

East Asian (EAS) AF: 0.000142 AC: 5 AN: 35224

South Asian (SAS) AF: 0.00 AC: 0 AN: 77876

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4956

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1071386

Other (OTH) AF: 0.00 AC: 0 AN: 57196

GnomAD4 genome AF: 0.0000201 AC: 3 AN: 149418 Hom.: 0 Cov.: 32 AF XY: 0.0000411 AC XY: 3 AN XY: 73038

African (AFR) AF: 0.00 AC: 0 AN: 40570

American (AMR) AF: 0.00 AC: 0 AN: 15076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3440

East Asian (EAS) AF: 0.000608 AC: 3 AN: 4934

South Asian (SAS) AF: 0.00 AC: 0 AN: 4628

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10374

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67146

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Generalized epilepsy-paroxysmal dyskinesia syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.8
Mutation Taster		=127/73	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs750804948; hg19: chr10-79397370;