17-50561545-G-A

Variant names:

• chr17-50561545-G-A
• rs752582722
• NM_018896.5:c.86G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018896.5(CACNA1G):​c.86G>A​(p.Gly29Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,387,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CACNA1G NM_018896.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20795116).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1G	NM_018896.5	MANE Select	c.86G>A	p.Gly29Glu	missense	Exon 1 of 38	NP_061496.2
	CACNA1G	NM_198377.3		c.86G>A	p.Gly29Glu	missense	Exon 1 of 37	NP_938191.2	O43497-20
	CACNA1G	NM_198396.3		c.86G>A	p.Gly29Glu	missense	Exon 1 of 36	NP_938406.1	O43497-33

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1G	ENST00000359106.10	TSL:1 MANE Select	c.86G>A	p.Gly29Glu	missense	Exon 1 of 38	ENSP00000352011.5	O43497-1
	CACNA1G	ENST00000507336.5	TSL:1	c.86G>A	p.Gly29Glu	missense	Exon 1 of 37	ENSP00000420918.1	O43497-20
	CACNA1G	ENST00000507510.6	TSL:1	c.86G>A	p.Gly29Glu	missense	Exon 1 of 37	ENSP00000423112.2	O43497-12

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000148 AC: 2 AN: 134926 AF XY: 0.0000270

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1387842 Hom.: 0 Cov.: 32 AF XY: 0.00000292 AC XY: 2 AN XY: 684962

African (AFR) AF: 0.00 AC: 0 AN: 31558

American (AMR) AF: 0.00 AC: 0 AN: 35712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25136

East Asian (EAS) AF: 0.00 AC: 0 AN: 35762

South Asian (SAS) AF: 0.0000252 AC: 2 AN: 79248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38638

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5094

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078872

Other (OTH) AF: 0.00 AC: 0 AN: 57822

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000105 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.00034	T
BayesDel_noAF	Benign	-0.11
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.21	T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	1.4	L
PhyloP100		2.1
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.28
Sift	Benign	0.099	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.17
MutPred		0.25		Gain of solvent accessibility (P = 0.0171)
MVP		0.73
MPC		1.7
ClinPred		0.20	T
GERP RS		1.8
PromoterAI		0.0041	Neutral
Varity_R		0.15
gMVP		0.51

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

Other links and lift over

dbSNP: rs752582722; hg19: chr17-48638906;