12-2053484-TA-T

Variant names:

• chr12-2053484-TA-T
• NM_000719.7:c.-77delA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_000719.7(CACNA1C):​c.-77delA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CACNA1C NM_000719.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.276

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 12-2053484-TA-T is Benign according to our data. Variant chr12-2053484-TA-T is described in ClinVar as [Benign]. Clinvar id is 1241429.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1C	NM_000719.7	c.-77delA		5_prime_UTR_variant	Exon 1 of 47	ENST00000399655.6	NP_000710.5
CACNA1C	NM_001167623.2	c.-77delA		5_prime_UTR_variant	Exon 1 of 47	ENST00000399603.6	NP_001161095.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1C	ENST00000399603	c.-77delA		5_prime_UTR_variant	Exon 1 of 47	5	NM_001167623.2	ENSP00000382512.1
CACNA1C	ENST00000399655	c.-77delA		5_prime_UTR_variant	Exon 1 of 47	1	NM_000719.7	ENSP00000382563.1
CACNA1C	ENST00000406454	c.-77delA		5_prime_UTR_variant	Exon 1 of 48	5		ENSP00000385896.3
CACNA1C	ENST00000399634	c.-77delA		5_prime_UTR_variant	Exon 1 of 47	5		ENSP00000382542.2
CACNA1C	ENST00000347598	c.-77delA		5_prime_UTR_variant	Exon 1 of 49	1		ENSP00000266376.6
CACNA1C	ENST00000327702	c.-77delA		5_prime_UTR_variant	Exon 1 of 48	1		ENSP00000329877.7
CACNA1C	ENST00000399617	c.-77delA		5_prime_UTR_variant	Exon 1 of 48	5		ENSP00000382526.1
CACNA1C	ENST00000335762	c.-77delA		5_prime_UTR_variant	Exon 1 of 48	5		ENSP00000336982.5
CACNA1C	ENST00000399641	c.-77delA		5_prime_UTR_variant	Exon 1 of 47	1		ENSP00000382549.1
CACNA1C	ENST00000682835	c.-77delA		5_prime_UTR_variant	Exon 1 of 47			ENSP00000507282.1
CACNA1C	ENST00000683482	c.-77delA		5_prime_UTR_variant	Exon 1 of 47			ENSP00000507169.1
CACNA1C	ENST00000682544.1	c.140-61738delA		intron_variant	Intron 1 of 49			ENSP00000507184.1
CACNA1C	ENST00000683824.1	c.140-61738delA		intron_variant	Intron 1 of 47			ENSP00000507867.1
CACNA1C	ENST00000682462.1	c.140-61738delA		intron_variant	Intron 1 of 46			ENSP00000507105.1
CACNA1C	ENST00000683781.1	c.140-61738delA		intron_variant	Intron 1 of 46			ENSP00000507434.1
CACNA1C	ENST00000683840.1	c.140-61738delA		intron_variant	Intron 1 of 46			ENSP00000507612.1
CACNA1C	ENST00000683956.1	c.140-61738delA		intron_variant	Intron 1 of 46			ENSP00000506882.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr12-2162650;