12-48826849-C-T

Variant summary

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

The NM_000725.4(CACNB3):​c.985C>T​(p.Pro329Ser) variant causes a missense 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: 32)

Consequence

CACNB3
NM_000725.4 missense

Scores

4
5
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.00
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/exons MANE UniProt
CACNB3NM_000725.4 linkuse as main transcriptc.985C>T p.Pro329Ser missense_variant 11/13 ENST00000301050.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CACNB3ENST00000301050.7 linkuse as main transcriptc.985C>T p.Pro329Ser missense_variant 11/131 NM_000725.4 P1P54284-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
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 GeneticsDec 15, 2022The c.985C>T (p.P329S) alteration is located in exon 11 (coding exon 11) of the CACNB3 gene. This alteration results from a C to T substitution at nucleotide position 985, causing the proline (P) at amino acid position 329 to be replaced by a serine (S). 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
Benign
0.082
BayesDel_addAF
Uncertain
0.054
T
BayesDel_noAF
Benign
-0.16
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.31
.;.;.;T;.
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.98
D;D;D;D;D
M_CAP
Benign
0.025
T
MetaRNN
Uncertain
0.55
D;D;D;D;D
MetaSVM
Benign
-0.82
T
MutationAssessor
Benign
1.5
.;.;.;L;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Pathogenic
-5.7
D;D;D;D;D
REVEL
Benign
0.28
Sift
Benign
0.080
T;T;T;T;D
Sift4G
Benign
0.20
T;T;T;T;T
Polyphen
0.99
.;.;.;D;.
Vest4
0.55
MutPred
0.61
.;.;.;Gain of catalytic residue at S332 (P = 0.0019);.;
MVP
0.75
MPC
1.3
ClinPred
0.98
D
GERP RS
5.4
Varity_R
0.31
gMVP
0.68

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: chr12-49220632; API