12-2053568-CAAT-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting

The NM_000719.7(CACNA1C):​c.7_9delAAT​(p.Asn3del) variant causes a conservative inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

CACNA1C
NM_000719.7 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.62
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_000719.7. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNA1CNM_000719.7 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 47 ENST00000399655.6 NP_000710.5 Q13936-12
CACNA1CNM_001167623.2 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 47 ENST00000399603.6 NP_001161095.1 Q13936-37

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACNA1CENST00000399603.6 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 47 5 NM_001167623.2 ENSP00000382512.1 Q13936-37
CACNA1CENST00000399655.6 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 47 1 NM_000719.7 ENSP00000382563.1 Q13936-12
CACNA1CENST00000406454.8 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 48 5 ENSP00000385896.3 F5GY28
CACNA1CENST00000399634.6 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 47 5 ENSP00000382542.2 E9PDI6
CACNA1CENST00000347598.9 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 49 1 ENSP00000266376.6 Q13936-11
CACNA1CENST00000344100.7 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 47 1 ENSP00000341092.3 Q13936-14
CACNA1CENST00000327702.12 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 48 1 ENSP00000329877.7 A0A0A0MR67
CACNA1CENST00000399617.6 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 48 5 ENSP00000382526.1 A0A0A0MSA1
CACNA1CENST00000399638.5 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 48 1 ENSP00000382547.1 Q13936-31
CACNA1CENST00000335762.10 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 48 5 ENSP00000336982.5 F5H522
CACNA1CENST00000399606.5 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 48 1 ENSP00000382515.1 Q13936-30
CACNA1CENST00000399621.5 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 47 1 ENSP00000382530.1 Q13936-24
CACNA1CENST00000399637.5 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 47 1 ENSP00000382546.1 Q13936-27
CACNA1CENST00000402845.7 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 47 1 ENSP00000385724.3 Q13936-13
CACNA1CENST00000399629.5 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 47 1 ENSP00000382537.1 Q13936-32
CACNA1CENST00000682336.1 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 47 ENSP00000507898.1 A0A804HKE9
CACNA1CENST00000399591.5 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 46 1 ENSP00000382500.1 Q13936-29
CACNA1CENST00000399595.5 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 46 1 ENSP00000382504.1 Q13936-25
CACNA1CENST00000399649.5 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 46 1 ENSP00000382557.1 Q13936-15
CACNA1CENST00000399597.5 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 47 1 ENSP00000382506.1 Q13936-22
CACNA1CENST00000399601.5 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 47 1 ENSP00000382510.1 Q13936-20
CACNA1CENST00000399641.6 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 47 1 ENSP00000382549.1 Q13936-23
CACNA1CENST00000399644.5 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 47 1 ENSP00000382552.1 Q13936-21
CACNA1CENST00000682835.1 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 47 ENSP00000507282.1 A0A804HIZ0
CACNA1CENST00000683482.1 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 47 ENSP00000507169.1 Q13936-35
CACNA1CENST00000682686.1 linkc.7_9delAAT p.Asn3del conservative_inframe_deletion Exon 1 of 46 ENSP00000507309.1 Q13936-19
CACNA1CENST00000682544.1 linkc.140-61655_140-61653delAAT intron_variant Intron 1 of 49 ENSP00000507184.1 A0A804HIR0
CACNA1CENST00000683824.1 linkc.140-61655_140-61653delAAT intron_variant Intron 1 of 47 ENSP00000507867.1 A0A804HKC4
CACNA1CENST00000682462.1 linkc.140-61655_140-61653delAAT intron_variant Intron 1 of 46 ENSP00000507105.1 A0A804HIJ8
CACNA1CENST00000683781.1 linkc.140-61655_140-61653delAAT intron_variant Intron 1 of 46 ENSP00000507434.1 A0A804HJB6
CACNA1CENST00000683840.1 linkc.140-61655_140-61653delAAT intron_variant Intron 1 of 46 ENSP00000507612.1 A0A804HJR1
CACNA1CENST00000683956.1 linkc.140-61655_140-61653delAAT intron_variant Intron 1 of 46 ENSP00000506882.1 A0A804HI37
CACNA1CENST00000480911.6 linkn.7_9delAAT non_coding_transcript_exon_variant Exon 1 of 27 5 ENSP00000437936.2 F5H638

Frequencies

GnomAD3 genomes
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
31

ClinVar

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

Submissions by phenotype

Cardiovascular phenotype Uncertain:1
Dec 11, 2020
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.7_9delAAT variant (also known as p.N3del) is located in coding exon 1 of the CACNA1C gene. This variant results from an in-frame AAT deletion at nucleotide positions 7 to 9. This results in the in-frame deletion of an asparagine at codon 3. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-2162734; API