GeneBe

rs1555881808

Positions:

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_000719.7(CACNA1C):​c.3202delG​(p.Glu1068fs) variant causes a frameshift 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 Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

CACNA1C
NM_000719.7 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.34
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CACNA1CNM_000719.7 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/47 ENST00000399655.6 NP_000710.5 Q13936-12
CACNA1CNM_001167623.2 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/47 ENST00000399603.6 NP_001161095.1 Q13936-37

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CACNA1CENST00000399603.6 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/475 NM_001167623.2 ENSP00000382512.1 Q13936-37
CACNA1CENST00000399655.6 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/471 NM_000719.7 ENSP00000382563.1 Q13936-12
CACNA1CENST00000682544.1 linkuse as main transcriptc.3352delG p.Glu1118fs frameshift_variant 26/50 ENSP00000507184.1 A0A804HIR0
CACNA1CENST00000406454.8 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/485 ENSP00000385896.3 F5GY28
CACNA1CENST00000399634.6 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/475 ENSP00000382542.2 E9PDI6
CACNA1CENST00000683824.1 linkuse as main transcriptc.3367delG p.Glu1123fs frameshift_variant 26/48 ENSP00000507867.1 A0A804HKC4
CACNA1CENST00000347598.9 linkuse as main transcriptc.3262delG p.Glu1088fs frameshift_variant 26/491 ENSP00000266376.6 Q13936-11
CACNA1CENST00000344100.7 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/471 ENSP00000341092.3 Q13936-14
CACNA1CENST00000327702.12 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/481 ENSP00000329877.7 A0A0A0MR67
CACNA1CENST00000399617.6 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/485 ENSP00000382526.1 A0A0A0MSA1
CACNA1CENST00000682462.1 linkuse as main transcriptc.3292delG p.Glu1098fs frameshift_variant 25/47 ENSP00000507105.1 A0A804HIJ8
CACNA1CENST00000683781.1 linkuse as main transcriptc.3292delG p.Glu1098fs frameshift_variant 25/47 ENSP00000507434.1 A0A804HJB6
CACNA1CENST00000683840.1 linkuse as main transcriptc.3292delG p.Glu1098fs frameshift_variant 25/47 ENSP00000507612.1 A0A804HJR1
CACNA1CENST00000683956.1 linkuse as main transcriptc.3292delG p.Glu1098fs frameshift_variant 25/47 ENSP00000506882.1 A0A804HI37
CACNA1CENST00000399638.5 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/481 ENSP00000382547.1 Q13936-31
CACNA1CENST00000335762.10 linkuse as main transcriptc.3277delG p.Glu1093fs frameshift_variant 26/485 ENSP00000336982.5 F5H522
CACNA1CENST00000399606.5 linkuse as main transcriptc.3262delG p.Glu1088fs frameshift_variant 26/481 ENSP00000382515.1 Q13936-30
CACNA1CENST00000399621.5 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/471 ENSP00000382530.1 Q13936-24
CACNA1CENST00000399637.5 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/471 ENSP00000382546.1 Q13936-27
CACNA1CENST00000402845.7 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/471 ENSP00000385724.3 Q13936-13
CACNA1CENST00000399629.5 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/471 ENSP00000382537.1 Q13936-32
CACNA1CENST00000682336.1 linkuse as main transcriptc.3277delG p.Glu1093fs frameshift_variant 26/47 ENSP00000507898.1 A0A804HKE9
CACNA1CENST00000399591.5 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/461 ENSP00000382500.1 Q13936-29
CACNA1CENST00000399595.5 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/461 ENSP00000382504.1 Q13936-25
CACNA1CENST00000399649.5 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/461 ENSP00000382557.1 Q13936-15
CACNA1CENST00000399597.5 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/471 ENSP00000382506.1 Q13936-22
CACNA1CENST00000399601.5 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/471 ENSP00000382510.1 Q13936-20
CACNA1CENST00000399641.6 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/471 ENSP00000382549.1 Q13936-23
CACNA1CENST00000399644.5 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/471 ENSP00000382552.1 Q13936-21
CACNA1CENST00000682835.1 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/47 ENSP00000507282.1 A0A804HIZ0
CACNA1CENST00000683482.1 linkuse as main transcriptc.3193delG p.Glu1065fs frameshift_variant 25/47 ENSP00000507169.1 Q13936-35
CACNA1CENST00000682686.1 linkuse as main transcriptc.3202delG p.Glu1068fs frameshift_variant 25/46 ENSP00000507309.1 Q13936-19
CACNA1CENST00000480911.6 linkuse as main transcriptn.*1809delG non_coding_transcript_exon_variant 23/275 ENSP00000437936.2 F5H638
CACNA1CENST00000480911.6 linkuse as main transcriptn.*1809delG 3_prime_UTR_variant 23/275 ENSP00000437936.2 F5H638

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 05, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1555881808; hg19: chr12-2715820; API