NM_001161352.2:c.90C>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4BP6_Moderate

The NM_001161352.2(KCNMA1):c.90C>A(p.His30Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000518 in 1,543,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H30R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

KCNMA1
NM_001161352.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.02

Publications

1 publications found

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 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)

KCNMA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3173522).

BP6

Variant 10-77637553-G-T is Benign according to our data. Variant chr10-77637553-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1019521.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KCNMA1	NM_001161352.2	MANE Select	c.90C>A	p.His30Gln	missense	Exon 1 of 28	NP_001154824.1
KCNMA1	NM_001437422.1		c.90C>A	p.His30Gln	missense	Exon 1 of 28	NP_001424351.1
KCNMA1	NM_001161353.2		c.90C>A	p.His30Gln	missense	Exon 1 of 28	NP_001154825.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
KCNMA1	ENST00000286628.14	TSL:1 MANE Select	c.90C>A	p.His30Gln	missense	Exon 1 of 28	ENSP00000286628.8
KCNMA1	ENST00000626620.3	TSL:1	c.90C>A	p.His30Gln	missense	Exon 1 of 28	ENSP00000485867.1
KCNMA1	ENST00000639406.1	TSL:1	c.90C>A	p.His30Gln	missense	Exon 1 of 29	ENSP00000491732.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000665

AC:

AN:

150326

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000118

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:

0.00000431

AC:

AN:

1391296

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

687120

show subpopulations

African (AFR)

AF:

0.0000317

AC:

AN:

31594

American (AMR)

AF:

0.0000277

AC:

AN:

36090

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25190

East Asian (EAS)

AF:

0.00

AC:

AN:

35908

South Asian (SAS)

AF:

0.00

AC:

AN:

79538

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44316

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5620

European-Non Finnish (NFE)

AF:

0.00000372

AC:

AN:

1075144

Other (OTH)

AF:

0.00

AC:

AN:

57896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152018

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41414

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5106

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67972

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Generalized epilepsy-paroxysmal dyskinesia syndrome

Benign:1

Jan 09, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.0074

Eigen

Benign

-0.0037

Eigen_PC

Benign

0.051

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.93

M_CAP

Pathogenic

0.79

MetaRNN

Benign

0.32

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

5.0

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.37

REVEL

Uncertain

0.31

Sift

Uncertain

0.0030

Sift4G

Benign

0.063

Polyphen

0.0

Vest4

0.25

MutPred

0.22

Gain of MoRF binding (P = 0.0854)

MVP

0.64

ClinPred

0.41

GERP RS

2.6

PromoterAI

-0.0011

Neutral

(source)

Varity_R

0.13

gMVP

0.35

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over