17-50561518-T-C

Variant summary

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

The NM_018896.5(CACNA1G):ā€‹c.59T>Cā€‹(p.Met20Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,385,040 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. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000022 ( 0 hom. )

Consequence

CACNA1G
NM_018896.5 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.120
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)

Genome browser will be placed here

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=0.09073618).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNA1GNM_018896.5 linkc.59T>C p.Met20Thr 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.59T>C p.Met20Thr missense_variant Exon 1 of 38 1 NM_018896.5 ENSP00000352011.5 O43497-1
CACNA1GENST00000507510.6 linkc.59T>C p.Met20Thr missense_variant Exon 1 of 37 1 ENSP00000423112.2 O43497-12

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000217
AC:
3
AN:
1385040
Hom.:
0
Cov.:
32
AF XY:
0.00000146
AC XY:
1
AN XY:
683540
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:
0.0000126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000185
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Apr 25, 2022
GeneDx
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Uncertain
0.013
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
11
DANN
Benign
0.76
DEOGEN2
Benign
0.0088
.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.
Eigen
Benign
-0.85
Eigen_PC
Benign
-0.76
FATHMM_MKL
Benign
0.29
N
LIST_S2
Benign
0.70
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
M_CAP
Pathogenic
0.39
D
MetaRNN
Benign
0.091
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
-0.27
T
MutationAssessor
Benign
0.0
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
Pathogenic
0.86
D
PROVEAN
Benign
-0.54
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
0.32
Sift
Benign
0.35
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
0.80
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
.;.;.;.;.;B;.;.;.;.;.;.;.;.;.;.;B;.;.;.;.;.;.;.;B;.
Vest4
0.081
MutPred
0.28
Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);Gain of phosphorylation at M20 (P = 0.0093);
MVP
0.52
MPC
1.4
ClinPred
0.034
T
GERP RS
0.50
Varity_R
0.065
gMVP
0.35

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: chr17-48638879; API