12-48823360-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000725.4(CACNB3):āc.62A>Gā(p.Tyr21Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,614,100 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000085 ( 0 hom., cov: 32)
Exomes š: 0.0000048 ( 0 hom. )
Consequence
CACNB3
NM_000725.4 missense
NM_000725.4 missense
Scores
4
10
5
Clinical Significance
Conservation
PhyloP100: 7.51
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 |
---|---|---|---|---|---|---|---|
CACNB3 | NM_000725.4 | c.62A>G | p.Tyr21Cys | missense_variant | 2/13 | ENST00000301050.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNB3 | ENST00000301050.7 | c.62A>G | p.Tyr21Cys | missense_variant | 2/13 | 1 | NM_000725.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152214Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251056Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135672
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461768Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727202
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GnomAD4 genome AF: 0.0000853 AC: 13AN: 152332Hom.: 0 Cov.: 32 AF XY: 0.0000805 AC XY: 6AN XY: 74490
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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 | Feb 27, 2024 | The c.62A>G (p.Y21C) alteration is located in exon 2 (coding exon 2) of the CACNB3 gene. This alteration results from a A to G substitution at nucleotide position 62, causing the tyrosine (Y) at amino acid position 21 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;.;.;D;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
.;.;.;N;.;N
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Uncertain
T;T;T;T;T;D
Polyphen
0.014
.;.;.;B;.;.
Vest4
MVP
MPC
0.58
ClinPred
D
GERP RS
Varity_R
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