NM_000725.4:c.392A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000725.4(CACNB3):​c.392A>G​(p.Gln131Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q131L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CACNB3
NM_000725.4 missense

Scores

2
10
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.31
Variant links:
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CACNB3NM_000725.4 linkc.392A>G p.Gln131Arg missense_variant Exon 4 of 13 ENST00000301050.7 NP_000716.2 P54284-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CACNB3ENST00000301050.7 linkc.392A>G p.Gln131Arg missense_variant Exon 4 of 13 1 NM_000725.4 ENSP00000301050.2 P54284-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1455388
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
723166
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Uncertain
0.10
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.26
.;.;.;T;.;.
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.91
D;D;D;D;D;D
M_CAP
Benign
0.034
D
MetaRNN
Uncertain
0.61
D;D;D;D;D;D
MetaSVM
Uncertain
0.35
D
MutationAssessor
Benign
1.5
.;.;.;L;.;.
PrimateAI
Uncertain
0.76
T
PROVEAN
Uncertain
-2.9
D;D;N;D;D;D
REVEL
Uncertain
0.58
Sift
Benign
0.078
T;T;T;T;T;T
Sift4G
Benign
0.15
T;T;T;T;T;T
Polyphen
0.94
.;.;.;P;.;.
Vest4
0.67
MutPred
0.32
.;.;Gain of MoRF binding (P = 0.0445);Gain of MoRF binding (P = 0.0445);.;.;
MVP
0.93
MPC
0.74
ClinPred
0.92
D
GERP RS
5.3
Varity_R
0.42
gMVP
0.61

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: rs372655713; hg19: chr12-49218141; COSMIC: COSV56400048; COSMIC: COSV56400048; API