17-50561536-C-T

Variant names:

• chr17-50561536-C-T
• rs947131228
• NM_018896.5:c.77C>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_018896.5(CACNA1G):​c.77C>T​(p.Ser26Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000176 in 1,537,864 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S26S) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: CACNA1G NM_018896.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1G	NM_018896.5	c.77C>T	p.Ser26Leu	missense_variant	Exon 1 of 38	ENST00000359106.10	NP_061496.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1G	ENST00000359106.10	c.77C>T	p.Ser26Leu	missense_variant	Exon 1 of 38	1	NM_018896.5	ENSP00000352011.5
CACNA1G	ENST00000507510.6	c.77C>T	p.Ser26Leu	missense_variant	Exon 1 of 37	1		ENSP00000423112.2

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151770 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000188 AC: 26 AN: 1386094 Hom.: 0 Cov.: 32 AF XY: 0.0000190 AC XY: 13 AN XY: 684036

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: 0.0000232

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151770 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74106

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.028	.;.;.;.;T;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;T;.
Eigen	Benign	0.19
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	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	0.81	D
MetaRNN	Uncertain	0.43	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	0.64	D
MutationAssessor	Benign	1.4	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	Pathogenic	0.90	D
PROVEAN	Benign	-1.9	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	0.45
Sift	Uncertain	0.0010	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	0.090	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		0.90, 1.0, 0.045	.;.;.;.;.;P;.;.;.;.;.;.;.;.;.;.;D;.;.;.;.;.;.;.;B;.
Vest4		0.33
MutPred		0.27		Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);Loss of phosphorylation at S26 (P = 0.0172);
MVP		0.86
MPC		1.7
ClinPred		0.87	D
GERP RS		2.8
Varity_R		0.25
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

Other links and lift over

dbSNP: rs947131228; hg19: chr17-48638897;