rs607458

Variant names:

• chr17-50561548-G-A
• rs607458
• NM_018896.5:c.89G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-50561548-G-A
• chr17-50561548-G-C
• chr17-50561548-G-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.89G>A​(p.Gly30Asp) 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 1,388,076 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CACNA1G NM_018896.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.13
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17914253).

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.89G>A	p.Gly30Asp	missense	Exon 1 of 38	NP_061496.2
	CACNA1G	NM_198377.3		c.89G>A	p.Gly30Asp	missense	Exon 1 of 37	NP_938191.2	O43497-20
	CACNA1G	NM_198396.3		c.89G>A	p.Gly30Asp	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.89G>A	p.Gly30Asp	missense	Exon 1 of 38	ENSP00000352011.5	O43497-1
	CACNA1G	ENST00000507336.5	TSL:1	c.89G>A	p.Gly30Asp	missense	Exon 1 of 37	ENSP00000420918.1	O43497-20
	CACNA1G	ENST00000507510.6	TSL:1	c.89G>A	p.Gly30Asp	missense	Exon 1 of 37	ENSP00000423112.2	O43497-12

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 135758 AF XY: 0.00

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: 1388076 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 685104

African (AFR) AF: 0.00 AC: 0 AN: 31566

American (AMR) AF: 0.00 AC: 0 AN: 35730

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25132

East Asian (EAS) AF: 0.00 AC: 0 AN: 35772

South Asian (SAS) AF: 0.00 AC: 0 AN: 79256

European-Finnish (FIN) AF: 0.0000514 AC: 2 AN: 38880

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5088

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078820

Other (OTH) AF: 0.00 AC: 0 AN: 57832

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.80	T
M_CAP	Pathogenic	0.67	D
MetaRNN	Benign	0.18	T
MetaSVM	Uncertain	0.019	D
MutationAssessor	Benign	1.1	L
PhyloP100		1.1
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.73	N
REVEL	Uncertain	0.31
Sift	Benign	0.20	T
Sift4G	Benign	0.82	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.17		Loss of methylation at R31 (P = 0.0418)
MVP		0.81
MPC		1.5
ClinPred		0.085	T
GERP RS		1.8
PromoterAI		-0.0038	Neutral
Varity_R		0.075
gMVP		0.49

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: rs607458; hg19: chr17-48638909;