NM_000725.4:c.392A>G

Variant names:

• chr12-48824358-A-G
• rs372655713
• 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 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CACNB3 NM_000725.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.31

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]

ACMG classification

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
CACNB3	NM_000725.4	c.392A>G	p.Gln131Arg	missense_variant	Exon 4 of 13	ENST00000301050.7	NP_000716.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNB3	ENST00000301050.7	c.392A>G	p.Gln131Arg	missense_variant	Exon 4 of 13	1	NM_000725.4	ENSP00000301050.2

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

Other links and lift over

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