Menu
GeneBe

3-54123552-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018398.3(CACNA2D3):c.162A>C(p.Lys54Asn) variant causes a missense 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CACNA2D3
NM_018398.3 missense

Scores

2
2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.38
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28853363).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CACNA2D3NM_018398.3 linkuse as main transcriptc.162A>C p.Lys54Asn missense_variant 2/38 ENST00000474759.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CACNA2D3ENST00000474759.6 linkuse as main transcriptc.162A>C p.Lys54Asn missense_variant 2/381 NM_018398.3 P1Q8IZS8-1
ENST00000666932.1 linkuse as main transcriptn.692T>G non_coding_transcript_exon_variant 2/3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 04, 2023The c.162A>C (p.K54N) alteration is located in exon 2 (coding exon 2) of the CACNA2D3 gene. This alteration results from a A to C substitution at nucleotide position 162, causing the lysine (K) at amino acid position 54 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.94
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
Cadd
Benign
21
Dann
Uncertain
0.99
DEOGEN2
Benign
0.081
T;T;T
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.029
FATHMM_MKL
Uncertain
0.82
D
M_CAP
Benign
0.0087
T
MetaRNN
Benign
0.29
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
L;L;L
MutationTaster
Benign
0.72
D;D;D;D
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-0.45
N;N;N
REVEL
Benign
0.048
Sift
Benign
0.29
T;T;T
Sift4G
Benign
0.30
T;T;T
Polyphen
0.0070
B;B;B
Vest4
0.63
MutPred
0.46
Loss of ubiquitination at K54 (P = 0.0233);Loss of ubiquitination at K54 (P = 0.0233);Loss of ubiquitination at K54 (P = 0.0233);
MVP
0.043
MPC
0.50
ClinPred
0.47
T
GERP RS
4.7
Varity_R
0.11
gMVP
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr3-54157579; API