rs79713097

Variant names:

• chr10-77112382-G-A
• rs79713097
• NM_001161352.2:c.945C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-77112382-G-A
• chr10-77112382-G-C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001161352.2(KCNMA1):​c.945C>T​(p.Ala315Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00274 in 1,613,564 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (16 hom.)
• Consequence: KCNMA1 NM_001161352.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.652
• Publications: 4 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Orphanet, Illumina
• Liang-Wang syndrome

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

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

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.131).
• BP6: Variant 10-77112382-G-A is Benign according to our data. Variant chr10-77112382-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 300969.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.652 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00294 (448/152302) while in subpopulation NFE AF = 0.00348 (237/68034). AF 95% confidence interval is 0.00312. There are 2 homozygotes in GnomAd4. There are 246 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMA1	NM_001161352.2	MANE Select	c.945C>T	p.Ala315Ala	synonymous	Exon 7 of 28	NP_001154824.1	Q12791-1
	KCNMA1	NM_001437422.1		c.1077C>T	p.Ala359Ala	synonymous	Exon 8 of 28	NP_001424351.1
	KCNMA1	NM_001161353.2		c.945C>T	p.Ala315Ala	synonymous	Exon 7 of 28	NP_001154825.1	Q12791-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNMA1	ENST00000286628.14	TSL:1 MANE Select	c.945C>T	p.Ala315Ala	synonymous	Exon 7 of 28	ENSP00000286628.8	Q12791-1
	KCNMA1	ENST00000626620.3	TSL:1	c.945C>T	p.Ala315Ala	synonymous	Exon 7 of 28	ENSP00000485867.1	Q12791-2
	KCNMA1	ENST00000639406.1	TSL:1	c.945C>T	p.Ala315Ala	synonymous	Exon 7 of 29	ENSP00000491732.1	B7ZMF5

Frequencies

GnomAD3 genomes AF: 0.00294 AC: 448 AN: 152184 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0161

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00348

Gnomad OTH AF: 0.000959

GnomAD2 exomes AF: 0.00337 AC: 848 AN: 251382 AF XY: 0.00318

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00685

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0165

Gnomad NFE exome AF: 0.00346

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00272 AC: 3975 AN: 1461262 Hom.: 16 Cov.: 30 AF XY: 0.00260 AC XY: 1890 AN XY: 726974

African (AFR) AF: 0.000269 AC: 9 AN: 33458

American (AMR) AF: 0.000313 AC: 14 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00628 AC: 164 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86236

European-Finnish (FIN) AF: 0.0151 AC: 806 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00253 AC: 2814 AN: 1111488

Other (OTH) AF: 0.00275 AC: 166 AN: 60368

GnomAD4 genome AF: 0.00294 AC: 448 AN: 152302 Hom.: 2 Cov.: 32 AF XY: 0.00330 AC XY: 246 AN XY: 74474

African (AFR) AF: 0.000385 AC: 16 AN: 41558

American (AMR) AF: 0.000327 AC: 5 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.0161 AC: 171 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00348 AC: 237 AN: 68034

Other (OTH) AF: 0.000949 AC: 2 AN: 2108

Alfa AF: 0.00276 Hom.: 1

Bravo AF: 0.00168

EpiCase AF: 0.00322

EpiControl AF: 0.00290

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Generalized epilepsy-paroxysmal dyskinesia syndrome (2)
-	-	1	KCNMA1-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	5.2
DANN	Benign	0.86
PhyloP100		0.65
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs79713097; hg19: chr10-78872140; COSMIC: COSV54237041;