17-50561541-G-T

Variant names:

• chr17-50561541-G-T
• rs1255435687
• NM_018896.5:c.82G>T

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.82G>T​(p.Ala28Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,386,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: CACNA1G NM_018896.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.147
• 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=0.22829396).

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.82G>T	p.Ala28Ser	missense	Exon 1 of 38	NP_061496.2
	CACNA1G	NM_198377.3		c.82G>T	p.Ala28Ser	missense	Exon 1 of 37	NP_938191.2	O43497-20
	CACNA1G	NM_198396.3		c.82G>T	p.Ala28Ser	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.82G>T	p.Ala28Ser	missense	Exon 1 of 38	ENSP00000352011.5	O43497-1
	CACNA1G	ENST00000507336.5	TSL:1	c.82G>T	p.Ala28Ser	missense	Exon 1 of 37	ENSP00000420918.1	O43497-20
	CACNA1G	ENST00000507510.6	TSL:1	c.82G>T	p.Ala28Ser	missense	Exon 1 of 37	ENSP00000423112.2	O43497-12

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000216 AC: 3 AN: 1386898 Hom.: 0 Cov.: 32 AF XY: 0.00000438 AC XY: 3 AN XY: 684438

African (AFR) AF: 0.00 AC: 0 AN: 31552

American (AMR) AF: 0.00 AC: 0 AN: 35690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25142

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38084

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5048

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1078616

Other (OTH) AF: 0.00 AC: 0 AN: 57810

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	0.082
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.87	D
M_CAP	Pathogenic	0.68	D
MetaRNN	Benign	0.23	T
MetaSVM	Uncertain	0.49	D
MutationAssessor	Benign	1.1	L
PhyloP100		0.15
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.46	N
REVEL	Uncertain	0.33
Sift	Benign	0.11	T
Sift4G	Benign	0.35	T
Polyphen		0.11	B
Vest4		0.13
MutPred		0.23		Gain of phosphorylation at A28 (P = 0.0068)
MVP		0.80
MPC		1.1
ClinPred		0.16	T
GERP RS		2.8
PromoterAI		-0.017	Neutral
Varity_R		0.064
gMVP		0.45
Mutation Taster		=81/19	polymorphism

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: rs1255435687; hg19: chr17-48638902;