17-50568971-G-T

Variant names:

• chr17-50568971-G-T
• NM_018896.5:c.344G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018896.5(CACNA1G):​c.344G>T​(p.Arg115Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,425,098 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CACNA1G NM_018896.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.38

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1G	NM_018896.5	c.344G>T	p.Arg115Leu	missense_variant	Exon 2 of 38	ENST00000359106.10	NP_061496.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1G	ENST00000359106.10	c.344G>T	p.Arg115Leu	missense_variant	Exon 2 of 38	1	NM_018896.5	ENSP00000352011.5
CACNA1G	ENST00000507510.6	c.344G>T	p.Arg115Leu	missense_variant	Exon 2 of 37	1		ENSP00000423112.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1425098 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 709866

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.22e-7

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	0.29
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.058	.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;D;.
Eigen	Benign	0.085
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	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	Uncertain	0.26	D
MetaRNN	Uncertain	0.59	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
MetaSVM	Pathogenic	0.88	D
MutationAssessor	Benign	1.6	L;L;L;L;.;L;L;L;L;L;L;L;L;L;L;L;L;L;L;L;L;L;L;L;L;L
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.5	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
REVEL	Pathogenic	0.74
Sift	Uncertain	0.014	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
Sift4G	Benign	0.085	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		0.41, 1.0, 0.0050	.;.;.;.;.;B;.;.;.;.;.;.;.;.;.;.;D;.;.;.;.;.;.;.;B;.
Vest4		0.52
MutPred		0.59		Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);Gain of catalytic residue at Q118 (P = 0.0987);
MVP		0.95
MPC		1.5
ClinPred		0.92	D
GERP RS		3.6
Varity_R		0.31
gMVP		0.72

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: chr17-48646332;