12-48818967-C-T

Variant summary

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

The NM_000725.4(CACNB3):​c.38C>T​(p.Ser13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,453,434 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: not found (cov: 31)
Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

CACNB3
NM_000725.4 missense

Scores

1
4
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.89
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31621552).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CACNB3NM_000725.4 linkuse as main transcriptc.38C>T p.Ser13Leu missense_variant 1/13 ENST00000301050.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CACNB3ENST00000301050.7 linkuse as main transcriptc.38C>T p.Ser13Leu missense_variant 1/131 NM_000725.4 P1P54284-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000275
AC:
4
AN:
1453434
Hom.:
0
Cov.:
33
AF XY:
0.00000415
AC XY:
3
AN XY:
722202
show subpopulations
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:
0.00000361
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

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 GeneticsNov 27, 2023The c.38C>T (p.S13L) alteration is located in exon 1 (coding exon 1) of the CACNB3 gene. This alteration results from a C to T substitution at nucleotide position 38, causing the serine (S) at amino acid position 13 to be replaced by a leucine (L). 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
0.18
BayesDel_addAF
Uncertain
0.041
T
BayesDel_noAF
Benign
-0.18
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.084
.;T;.;.
Eigen
Benign
0.11
Eigen_PC
Benign
0.15
FATHMM_MKL
Benign
0.64
D
LIST_S2
Uncertain
0.95
D;D;D;D
M_CAP
Pathogenic
0.91
D
MetaRNN
Benign
0.32
T;T;T;T
MetaSVM
Benign
-0.59
T
MutationAssessor
Benign
1.1
.;L;.;L
MutationTaster
Benign
0.98
D;D;D;D;D
PROVEAN
Benign
-0.48
N;N;N;N
REVEL
Benign
0.19
Sift
Uncertain
0.0050
D;D;T;D
Sift4G
Benign
0.37
T;T;T;T
Polyphen
0.89
.;P;.;.
Vest4
0.23
MutPred
0.23
Loss of glycosylation at S13 (P = 0.0044);Loss of glycosylation at S13 (P = 0.0044);Loss of glycosylation at S13 (P = 0.0044);Loss of glycosylation at S13 (P = 0.0044);
MVP
0.81
MPC
0.43
ClinPred
0.69
D
GERP RS
3.4
Varity_R
0.29
gMVP
0.37

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: chr12-49212750; API