rs768014195

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018896.5(CACNA1G):​c.28G>A​(p.Ala10Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,382,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CACNA1G
NM_018896.5 missense

Scores

1
5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.397
Variant links:
Genes affected
CACNA1G (HGNC:1394): (calcium voltage-gated channel subunit alpha1 G) Voltage-sensitive calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division, and cell death. This gene encodes a T-type, low-voltage activated calcium channel. The T-type channels generate currents that are both transient, owing to fast inactivation, and tiny, owing to small conductance. T-type channels are thought to be involved in pacemaker activity, low-threshold calcium spikes, neuronal oscillations and resonance, and rebound burst firing. Many alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Sep 2011]
CACNA1G-AS1 (HGNC:27377): (CACNA1G antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08661175).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNA1GNM_018896.5 linkc.28G>A p.Ala10Thr missense_variant Exon 1 of 38 ENST00000359106.10 NP_061496.2 O43497-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACNA1GENST00000359106.10 linkc.28G>A p.Ala10Thr missense_variant Exon 1 of 38 1 NM_018896.5 ENSP00000352011.5 O43497-1
CACNA1GENST00000507510.6 linkc.28G>A p.Ala10Thr missense_variant Exon 1 of 37 1 ENSP00000423112.2 O43497-12

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000145
AC:
2
AN:
1382860
Hom.:
0
Cov.:
32
AF XY:
0.00000293
AC XY:
2
AN XY:
682514
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000253
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.070
BayesDel_addAF
Benign
-0.018
T
BayesDel_noAF
Benign
-0.26
CADD
Benign
13
DANN
Uncertain
0.99
DEOGEN2
Benign
0.019
.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.
Eigen
Benign
-0.82
Eigen_PC
Benign
-0.75
FATHMM_MKL
Benign
0.51
D
LIST_S2
Uncertain
0.89
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
Pathogenic
0.57
D
MetaRNN
Benign
0.087
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
-0.26
T
MutationAssessor
Benign
0.55
N;N;N;N;.;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-0.77
N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL
Uncertain
0.33
Sift
Benign
1.0
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G
Benign
0.20
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.0, 0.0010
.;.;.;.;.;B;.;.;.;.;.;.;.;.;.;.;B;.;.;.;.;.;.;.;B;.
Vest4
0.050
MutPred
0.12
Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);Gain of phosphorylation at A10 (P = 0.0209);
MVP
0.58
MPC
1.2
ClinPred
0.063
T
GERP RS
-2.0
Varity_R
0.049
gMVP
0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-48638848; API