Genetic Variant CACNA1G:p.Gly35Arg (chr17-50561562-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018896.5(CACNA1G):c.103G>C(p.Gly35Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000717 in 1,395,558 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

CACNA1G
NM_018896.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.30

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018896.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CACNA1G	NM_018896.5	MANE Select	c.103G>C	p.Gly35Arg	missense	Exon 1 of 38	NP_061496.2
CACNA1G	NM_198377.3		c.103G>C	p.Gly35Arg	missense	Exon 1 of 37	NP_938191.2	O43497-20
CACNA1G	NM_198396.3		c.103G>C	p.Gly35Arg	missense	Exon 1 of 36	NP_938406.1	O43497-33

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CACNA1G	ENST00000359106.10	TSL:1 MANE Select	c.103G>C	p.Gly35Arg	missense	Exon 1 of 38	ENSP00000352011.5	O43497-1
CACNA1G	ENST00000507336.5	TSL:1	c.103G>C	p.Gly35Arg	missense	Exon 1 of 37	ENSP00000420918.1	O43497-20
CACNA1G	ENST00000507510.6	TSL:1	c.103G>C	p.Gly35Arg	missense	Exon 1 of 37	ENSP00000423112.2	O43497-12

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.17e-7

AC:

AN:

1395558

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689176

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31780

American (AMR)

AF:

0.0000277

AC:

AN:

36068

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25180

East Asian (EAS)

AF:

0.00

AC:

AN:

36040

South Asian (SAS)

AF:

0.00

AC:

AN:

79710

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41726

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5272

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1081736

Other (OTH)

AF:

0.00

AC:

AN:

58046

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.16

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.88

M_CAP

Pathogenic

0.81

MetaRNN

Uncertain

0.45

MetaSVM

Uncertain

0.79

MutationAssessor

Benign

1.4

PhyloP100

5.3

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.52

Sift

Uncertain

0.015

Sift4G

Benign

0.38

Polyphen

1.0

Vest4

0.42

MutPred

0.26

Gain of MoRF binding (P = 0.0354)

MVP

0.92

MPC

2.6

ClinPred

0.76

GERP RS

1.8

PromoterAI

-0.015

Neutral

(source)

Varity_R

0.15

gMVP

0.55

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over