chr22-39570820-C-G

Variant names:

• chr22-39570820-C-G
• rs748236821
• NM_021096.4:c.68C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021096.4(CACNA1I):​c.68C>G​(p.Thr23Arg) 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.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CACNA1I NM_021096.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.935

Genes affected

CACNA1I (HGNC:1396): (calcium voltage-gated channel subunit alpha1 I) This gene encodes the pore-forming alpha subunit of a voltage gated calcium channel. The encoded protein is a member of a subfamily of calcium channels referred to as is a low voltage-activated, T-type, calcium channel. The channel encoded by this protein is characterized by a slower activation and inactivation compared to other T-type calcium channels. This protein may be involved in calcium signaling in neurons. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21257693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1I	NM_021096.4	c.68C>G	p.Thr23Arg	missense_variant	Exon 1 of 37	ENST00000402142.4	NP_066919.2
CACNA1I	NM_001003406.2	c.68C>G	p.Thr23Arg	missense_variant	Exon 1 of 36		NP_001003406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1I	ENST00000402142.4	c.68C>G	p.Thr23Arg	missense_variant	Exon 1 of 37	1	NM_021096.4	ENSP00000385019.3
CACNA1I	ENST00000404898.5	c.68C>G	p.Thr23Arg	missense_variant	Exon 1 of 36	1		ENSP00000384093.1
CACNA1I	ENST00000401624.5	c.68C>G	p.Thr23Arg	missense_variant	Exon 1 of 36	1		ENSP00000383887.1
CACNA1I	ENST00000407673.5	c.68C>G	p.Thr23Arg	missense_variant	Exon 1 of 35	1		ENSP00000385680.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	.;.;.;T
Eigen	Benign	-0.095
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.41	T;T;T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Uncertain	0.30	D
MutationAssessor	Benign	1.1	L;L;L;L
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.27	N;N;N;N
REVEL	Uncertain	0.29
Sift	Benign	0.12	T;T;T;T
Sift4G	Benign	0.53	T;T;T;T
Polyphen		0.97, 0.94	.;.;D;P
Vest4		0.14
MutPred		0.32		Loss of glycosylation at T23 (P = 0.0041);Loss of glycosylation at T23 (P = 0.0041);Loss of glycosylation at T23 (P = 0.0041);Loss of glycosylation at T23 (P = 0.0041);
MVP		0.71
MPC		1.6
ClinPred		0.41	T
GERP RS		5.3
Varity_R		0.070
gMVP		0.46

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: rs748236821; hg19: chr22-39966825;