NM_001161352.2:c.*1571C>T

Variant names:

• chr10-76885695-G-A
• rs10762733
• NM_001161352.2:c.*1571C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001161352.2(KCNMA1):​c.*1571C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 984,658 control chromosomes in the GnomAD database, including 151,938 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (19488 hom., cov: 31)
  • Exomes 𝑓: 0.56 (132450 hom.)
• Consequence: KCNMA1 NM_001161352.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.252
• Publications: 7 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, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 10-76885695-G-A is Benign according to our data. Variant chr10-76885695-G-A is described in ClinVar as Benign. ClinVar VariationId is 300933.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

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.*1571C>T		3_prime_UTR	Exon 28 of 28	NP_001154824.1	Q12791-1
	KCNMA1	NM_001437422.1		c.*1571C>T		3_prime_UTR	Exon 28 of 28	NP_001424351.1
	KCNMA1	NM_001161353.2		c.*1571C>T		3_prime_UTR	Exon 28 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.*1571C>T		3_prime_UTR	Exon 28 of 28	ENSP00000286628.8	Q12791-1
	KCNMA1	ENST00000639406.1	TSL:1	c.*1571C>T		3_prime_UTR	Exon 29 of 29	ENSP00000491732.1	B7ZMF5
	KCNMA1	ENST00000286627.10	TSL:1	c.*1571C>T		3_prime_UTR	Exon 27 of 27	ENSP00000286627.5	Q12791-5

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75009 AN: 151776 Hom.: 19479 Cov.: 31

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.519

GnomAD4 exome AF: 0.562 AC: 467923 AN: 832764 Hom.: 132450 Cov.: 32 AF XY: 0.562 AC XY: 216310 AN XY: 384588

African (AFR) AF: 0.366 AC: 5783 AN: 15780

American (AMR) AF: 0.354 AC: 347 AN: 980

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 3329 AN: 5152

East Asian (EAS) AF: 0.285 AC: 1033 AN: 3630

South Asian (SAS) AF: 0.381 AC: 6266 AN: 16452

European-Finnish (FIN) AF: 0.623 AC: 172 AN: 276

Middle Eastern (MID) AF: 0.562 AC: 910 AN: 1620

European-Non Finnish (NFE) AF: 0.572 AC: 435538 AN: 761584

Other (OTH) AF: 0.533 AC: 14545 AN: 27290

GnomAD4 genome AF: 0.494 AC: 75032 AN: 151894 Hom.: 19488 Cov.: 31 AF XY: 0.487 AC XY: 36163 AN XY: 74218

African (AFR) AF: 0.382 AC: 15817 AN: 41382

American (AMR) AF: 0.416 AC: 6353 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2229 AN: 3470

East Asian (EAS) AF: 0.300 AC: 1550 AN: 5160

South Asian (SAS) AF: 0.357 AC: 1715 AN: 4798

European-Finnish (FIN) AF: 0.580 AC: 6116 AN: 10546

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39437 AN: 67952

Other (OTH) AF: 0.516 AC: 1089 AN: 2110

Alfa AF: 0.554 Hom.: 27532

Bravo AF: 0.477

Asia WGS AF: 0.314 AC: 1092 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Generalized epilepsy-paroxysmal dyskinesia syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.87
DANN	Benign	0.69
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10762733; hg19: chr10-78645453;