Genetic Variant CACNA2D3:c.-113C>T (chr3-54123560-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000490478.5(CACNA2D3):c.-113C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,613,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

CACNA2D3
ENST00000490478.5 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.49

Publications

1 publications found

Variant links:

Genes affected

CACNA2D3 (HGNC:15460): (calcium voltage-gated channel auxiliary subunit alpha2delta 3) This gene encodes a member of the alpha-2/delta subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Various versions of each of these subunits exist, either expressed from similar genes or the result of alternative splicing. Research on a highly similar protein in rabbit suggests the protein described in this record is cleaved into alpha-2 and delta subunits. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

CACNA2D3 links:

ENSG00000286353 (HGNC:):

ENSG00000286353 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08792058).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000490478.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA2D3	NM_018398.3	MANE Select	c.170C>T	p.Ala57Val	missense	Exon 2 of 38	NP_060868.2	Q8IZS8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CACNA2D3	ENST00000490478.5	TSL:1	c.-113C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 37	ENSP00000417279.1	Q8IZS8-2
CACNA2D3	ENST00000474759.6	TSL:1 MANE Select	c.170C>T	p.Ala57Val	missense	Exon 2 of 38	ENSP00000419101.1	Q8IZS8-1
CACNA2D3	ENST00000490478.5	TSL:1	c.-113C>T		5_prime_UTR	Exon 1 of 37	ENSP00000417279.1	Q8IZS8-2

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000128

AC:

AN:

249302

AF XY:

0.000155

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000212

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000144

AC:

210

AN:

1461646

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

107

AN XY:

727112

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.000268

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000161

AC:

179

AN:

1111810

Other (OTH)

AF:

0.000315

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000151

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41512

American (AMR)

AF:

0.000719

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000134

Hom.:

Bravo

AF:

0.000155

ExAC

AF:

0.0000993

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000415

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.17

Eigen_PC

Benign

0.044

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0065

MetaRNN

Benign

0.088

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.73

PhyloP100

7.5

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.22

REVEL

Benign

0.12

Sift

Benign

0.32

Sift4G

Benign

0.29

Polyphen

0.0090

Vest4

0.55

MutPred

0.47

Loss of disorder (P = 0.0647)

MVP

0.068

MPC

0.32

ClinPred

0.12

GERP RS

5.0

PromoterAI

-0.029

Neutral

(source)

Varity_R

0.095

gMVP

0.58

Mutation Taster

=81/19

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over