3-54122748-G-C

Variant names:

• chr3-54122748-G-C
• NM_018398.3:c.35G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018398.3(CACNA2D3):​c.35G>C​(p.Arg12Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000938 in 1,066,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 9.4e-7 (0 hom.)
• Consequence: CACNA2D3 NM_018398.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.75

Genes affected

CACNA2D3 (HGNC:15460): (calcium voltage-gated channel auxiliary subunit alpha2delta 3) This gene encodes a member of the alpha-2/delta subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Various versions of each of these subunits exist, either expressed from similar genes or the result of alternative splicing. Research on a highly similar protein in rabbit suggests the protein described in this record is cleaved into alpha-2 and delta subunits. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

ENSG00000286353 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18968159).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA2D3	NM_018398.3	c.35G>C	p.Arg12Pro	missense_variant	Exon 1 of 38	ENST00000474759.6	NP_060868.2
LOC124909381	XR_007095914.1	n.386+309C>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA2D3	ENST00000474759.6	c.35G>C	p.Arg12Pro	missense_variant	Exon 1 of 38	1	NM_018398.3	ENSP00000419101.1
ENSG00000286353	ENST00000666932.1	n.1187+309C>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 9.38e-7 AC: 1 AN: 1066146 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 503368

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: 0.00000110

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.053	T;T;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.44	.;T;.
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.40	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.18	T;T;T
Polyphen		0.089	B;B;B
Vest4		0.33
MutPred		0.45		Loss of MoRF binding (P = 3e-04);Loss of MoRF binding (P = 3e-04);Loss of MoRF binding (P = 3e-04);
MVP		0.21
MPC		0.38
ClinPred		0.49	T
GERP RS		4.2
Varity_R		0.36
gMVP		0.41

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: chr3-54156775;