chr10-77086567-G-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_001161352.2(KCNMA1):c.1361C>T(p.Ala454Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Consequence
KCNMA1
NM_001161352.2 missense
NM_001161352.2 missense
Scores
7
7
5
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 10.0
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KCNMA1. . Gene score misZ: 5.0622 (greater than the threshold 3.09). Trascript score misZ: 6.5162 (greater than threshold 3.09). The gene has 12 curated pathogenic missense variants (we use a threshold of 10). The gene has 25 curated benign missense variants. GenCC has associacion of the gene with cerebellar atrophy, developmental delay, and seizures, generalized epilepsy-paroxysmal dyskinesia syndrome, Liang-Wang syndrome.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;T;.;.;.;.;.;.;.;.;.;.;.;.;.
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;L;L;L;.;.;.;.;L;.;.;.;L;L;L;.;.;.
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
.;.;.;.;.;.;.;.;D;.;.;.;.;.;.;.;.;.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
REVEL
Uncertain
Sift
Uncertain
.;.;.;.;.;.;.;.;D;.;.;.;.;.;.;.;.;.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Sift4G
Uncertain
D;.;.;.;.;.;.;.;D;.;.;.;.;.;.;.;D;.;D;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;D;D;D;.;.;.;.;.;.;D;.;.;.;.;.
Polyphen
0.90, 1.0, 0.88, 1.0, 0.80
.;.;.;.;.;.;.;.;P;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;P;D;.;.;.;.;D;P;.;.;P;.;.;.;.;.
Vest4
0.75, 0.75, 0.73, 0.73, 0.67, 0.75, 0.56, 0.65
MutPred
0.38
.;Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);.;Gain of ubiquitination at K457 (P = 0.0913);.;Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);.;.;Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);.;.;.;.;.;.;Gain of ubiquitination at K457 (P = 0.0913);.;Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);.;.;.;Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);.;Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);Gain of ubiquitination at K457 (P = 0.0913);.;.;Gain of ubiquitination at K457 (P = 0.0913);
MVP
MPC
1.8
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at