17-50561548-G-C

Variant names:

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

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>C​(p.Gly30Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. G30D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CACNA1G NM_018896.5 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.22025448).

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>C	p.Gly30Ala	missense	Exon 1 of 38	NP_061496.2
	CACNA1G	NM_198377.3		c.89G>C	p.Gly30Ala	missense	Exon 1 of 37	NP_938191.2	O43497-20
	CACNA1G	NM_198396.3		c.89G>C	p.Gly30Ala	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>C	p.Gly30Ala	missense	Exon 1 of 38	ENSP00000352011.5	O43497-1
	CACNA1G	ENST00000507336.5	TSL:1	c.89G>C	p.Gly30Ala	missense	Exon 1 of 37	ENSP00000420918.1	O43497-20
	CACNA1G	ENST00000507510.6	TSL:1	c.89G>C	p.Gly30Ala	missense	Exon 1 of 37	ENSP00000423112.2	O43497-12

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.79	T
M_CAP	Pathogenic	0.79	D
MetaRNN	Benign	0.22	T
MetaSVM	Uncertain	0.20	D
MutationAssessor	Benign	1.1	L
PhyloP100		1.1
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.85	N
REVEL	Uncertain	0.30
Sift	Benign	0.18	T
Sift4G	Benign	0.46	T
Polyphen		0.018	B
Vest4		0.18
MutPred		0.14		Loss of methylation at R31 (P = 0.0657)
MVP		0.80
MPC		1.3
ClinPred		0.078	T
GERP RS		1.8
PromoterAI		0.015	Neutral
Varity_R		0.081
gMVP		0.50

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;