12-2605102-G-A

Variant names:

• chr12-2605102-G-A
• NM_000719.7:c.2982G>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_000719.7(CACNA1C):​c.2982G>A​(p.Val994Val) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CACNA1C NM_000719.7 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.20

Genes affected

CACNA1C (HGNC:1390): (calcium voltage-gated channel subunit alpha1 C) This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. The alpha-1 subunit consists of 24 transmembrane segments and forms the pore through which ions pass into the cell. The calcium channel consists of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. There are multiple isoforms of each of these proteins, either encoded by different genes or the result of alternative splicing of transcripts. The protein encoded by this gene binds to and is inhibited by dihydropyridine. Alternative splicing results in many transcript variants encoding different proteins. Some of the predicted proteins may not produce functional ion channel subunits. [provided by RefSeq, Oct 2012]

CACNA1C-AS3 (HGNC:40117): (CACNA1C antisense RNA 3)

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 12-2605102-G-A is Benign according to our data. Variant chr12-2605102-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3716611.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.2 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1C	NM_000719.7	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 47	ENST00000399655.6	NP_000710.5
CACNA1C	NM_001167623.2	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 47	ENST00000399603.6	NP_001161095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1C	ENST00000399603.6	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 47	5	NM_001167623.2	ENSP00000382512.1
CACNA1C	ENST00000399655.6	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 47	1	NM_000719.7	ENSP00000382563.1
CACNA1C	ENST00000682544.1	c.3132G>A	p.Val1044Val	synonymous_variant	Exon 24 of 50			ENSP00000507184.1
CACNA1C	ENST00000406454.8	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 48	5		ENSP00000385896.3
CACNA1C	ENST00000399634.6	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 47	5		ENSP00000382542.2
CACNA1C	ENST00000683824.1	c.3147G>A	p.Val1049Val	synonymous_variant	Exon 24 of 48			ENSP00000507867.1
CACNA1C	ENST00000347598.9	c.3042G>A	p.Val1014Val	synonymous_variant	Exon 24 of 49	1		ENSP00000266376.6
CACNA1C	ENST00000344100.7	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 47	1		ENSP00000341092.3
CACNA1C	ENST00000327702.12	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 48	1		ENSP00000329877.7
CACNA1C	ENST00000399617.6	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 48	5		ENSP00000382526.1
CACNA1C	ENST00000682462.1	c.3072G>A	p.Val1024Val	synonymous_variant	Exon 23 of 47			ENSP00000507105.1
CACNA1C	ENST00000683781.1	c.3072G>A	p.Val1024Val	synonymous_variant	Exon 23 of 47			ENSP00000507434.1
CACNA1C	ENST00000683840.1	c.3072G>A	p.Val1024Val	synonymous_variant	Exon 23 of 47			ENSP00000507612.1
CACNA1C	ENST00000683956.1	c.3072G>A	p.Val1024Val	synonymous_variant	Exon 23 of 47			ENSP00000506882.1
CACNA1C	ENST00000399638.5	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 48	1		ENSP00000382547.1
CACNA1C	ENST00000335762.10	c.3057G>A	p.Val1019Val	synonymous_variant	Exon 24 of 48	5		ENSP00000336982.5
CACNA1C	ENST00000399606.5	c.3042G>A	p.Val1014Val	synonymous_variant	Exon 24 of 48	1		ENSP00000382515.1
CACNA1C	ENST00000399621.5	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 47	1		ENSP00000382530.1
CACNA1C	ENST00000399637.5	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 47	1		ENSP00000382546.1
CACNA1C	ENST00000402845.7	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 47	1		ENSP00000385724.3
CACNA1C	ENST00000399629.5	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 47	1		ENSP00000382537.1
CACNA1C	ENST00000682336.1	c.3057G>A	p.Val1019Val	synonymous_variant	Exon 24 of 47			ENSP00000507898.1
CACNA1C	ENST00000399591.5	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 46	1		ENSP00000382500.1
CACNA1C	ENST00000399595.5	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 46	1		ENSP00000382504.1
CACNA1C	ENST00000399649.5	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 46	1		ENSP00000382557.1
CACNA1C	ENST00000399597.5	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 47	1		ENSP00000382506.1
CACNA1C	ENST00000399601.5	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 47	1		ENSP00000382510.1
CACNA1C	ENST00000399641.6	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 47	1		ENSP00000382549.1
CACNA1C	ENST00000399644.5	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 47	1		ENSP00000382552.1
CACNA1C	ENST00000682835.1	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 47			ENSP00000507282.1
CACNA1C	ENST00000683482.1	c.2973G>A	p.Val991Val	synonymous_variant	Exon 23 of 47			ENSP00000507169.1
CACNA1C	ENST00000682686.1	c.2982G>A	p.Val994Val	synonymous_variant	Exon 23 of 46			ENSP00000507309.1
CACNA1C	ENST00000480911.6	n.*1589G>A		non_coding_transcript_exon_variant	Exon 21 of 27	5		ENSP00000437936.2
CACNA1C	ENST00000480911.6	n.*1589G>A		3_prime_UTR_variant	Exon 21 of 27	5		ENSP00000437936.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Long QT syndrome Benign:1

Feb 05, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	8.6
DANN	Benign	0.85

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-2714268; COSMIC: COSV59707355; COSMIC: COSV59707355;