NM_018896.5:c.155C>T

Variant names:

• chr17-50561614-C-T
• rs1303318542
• NM_018896.5:c.155C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018896.5(CACNA1G):​c.155C>T​(p.Pro52Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000347 in 1,441,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P52R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: CACNA1G NM_018896.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.53
• Publications: 1 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3427322).

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.155C>T	p.Pro52Leu	missense	Exon 1 of 38	NP_061496.2
	CACNA1G	NM_198377.3		c.155C>T	p.Pro52Leu	missense	Exon 1 of 37	NP_938191.2	O43497-20
	CACNA1G	NM_198396.3		c.155C>T	p.Pro52Leu	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.155C>T	p.Pro52Leu	missense	Exon 1 of 38	ENSP00000352011.5	O43497-1
	CACNA1G	ENST00000507336.5	TSL:1	c.155C>T	p.Pro52Leu	missense	Exon 1 of 37	ENSP00000420918.1	O43497-20
	CACNA1G	ENST00000507510.6	TSL:1	c.155C>T	p.Pro52Leu	missense	Exon 1 of 37	ENSP00000423112.2	O43497-12

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000970 AC: 2 AN: 206138 AF XY: 0.0000175

Gnomad AFR exome AF: 0.0000890

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: 0.0000114

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000347 AC: 5 AN: 1441338 Hom.: 0 Cov.: 32 AF XY: 0.00000559 AC XY: 4 AN XY: 715102

African (AFR) AF: 0.0000302 AC: 1 AN: 33154

American (AMR) AF: 0.00 AC: 0 AN: 42226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25772

East Asian (EAS) AF: 0.00 AC: 0 AN: 38792

South Asian (SAS) AF: 0.00 AC: 0 AN: 83760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5662

European-Non Finnish (NFE) AF: 0.00000363 AC: 4 AN: 1103326

Other (OTH) AF: 0.00 AC: 0 AN: 59540

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.44	D
MetaRNN	Benign	0.34	T
MetaSVM	Uncertain	0.49	D
MutationAssessor	Benign	1.5	L
PhyloP100		3.5
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-6.3	D
REVEL	Uncertain	0.56
Sift	Benign	0.071	T
Sift4G	Benign	0.12	T
Polyphen		0.17	B
Vest4		0.23
MutPred		0.34		Loss of disorder (P = 0.0278)
MVP		0.93
MPC		1.3
ClinPred		0.38	T
GERP RS		2.8
PromoterAI		-0.018	Neutral
Varity_R		0.27
gMVP		0.77
Mutation Taster		=53/47	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: rs1303318542; hg19: chr17-48638975;