12-48825725-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_000725.4(CACNB3):c.698G>A(p.Gly233Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,614,066 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 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
CACNB3
NM_000725.4 missense
NM_000725.4 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 5.63
Genes affected
CACNB3 (HGNC:1403): (calcium voltage-gated channel auxiliary subunit beta 3) This gene encodes a regulatory beta subunit of the voltage-dependent calcium channel. Beta subunits are composed of five domains, which contribute to the regulation of surface expression and gating of calcium channels and may also play a role in the regulation of transcription factors and calcium transport. [provided by RefSeq, Oct 2011]
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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=0.34346253).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNB3 | NM_000725.4 | c.698G>A | p.Gly233Asp | missense_variant | 9/13 | ENST00000301050.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNB3 | ENST00000301050.7 | c.698G>A | p.Gly233Asp | missense_variant | 9/13 | 1 | NM_000725.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152232Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461834Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727228
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74372
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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 submitter | clinical testing | Ambry Genetics | Mar 25, 2024 | The c.698G>A (p.G233D) alteration is located in exon 9 (coding exon 9) of the CACNB3 gene. This alteration results from a G to A substitution at nucleotide position 698, causing the glycine (G) at amino acid position 233 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;.;.;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;.;.;L;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Benign
T;T;T;T;T;T
Polyphen
0.95
.;.;.;.;P;.
Vest4
MutPred
0.48
.;.;.;.;Loss of loop (P = 0.0112);.;
MVP
MPC
1.3
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at