Variant 17-50561527-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018896.5(CACNA1G):c.68A>G(p.Asn23Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000026 in 1,537,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

CACNA1G
NM_018896.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.628

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 links:

CACNA1G-AS1 (HGNC:27377): (CACNA1G antisense RNA 1)

CACNA1G-AS1 links:

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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=0.17389497).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1G	NM_018896.5 link	c.68A>G	p.Asn23Ser	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
CACNA1G	ENST00000359106.10 link	c.68A>G	p.Asn23Ser	missense_variant	Exon 1 of 38	1	NM_018896.5	ENSP00000352011.5		O43497-1
CACNA1G	ENST00000507510.6 link	c.68A>G	p.Asn23Ser	missense_variant	Exon 1 of 37	1		ENSP00000423112.2		O43497-12

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151850

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

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

GnomAD3 exomes

AF:

0.0000149

AC:

AN:

134676

Hom.:

AF XY:

0.00

AC XY:

AN XY:

73704

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000954

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000197

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000217

AC:

AN:

1385644

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

683806

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.27e-7

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151850

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74160

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.091

FATHMM_MKL

Benign

0.60

LIST_S2

Pathogenic

0.97

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

0.61

MetaRNN

Benign

0.17

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

0.52

MutationAssessor

Benign

0.46

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

0.89

PROVEAN

Benign

-0.80

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

Benign

0.27

Sift

Benign

0.21

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

0.94

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

0.87, 0.99, 0.0

.;.;.;.;.;P;.;.;.;.;.;.;.;.;.;.;D;.;.;.;.;.;.;.;B;.

Vest4

0.066

MutPred

0.18

Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);Gain of phosphorylation at N23 (P = 0.0065);

MVP

0.87

MPC

1.4

ClinPred

0.15

GERP RS

2.8

Varity_R

0.077

gMVP

0.58

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over