chr3-54581847-T-G
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_018398.3(CACNA2D3):c.933T>G(p.Thr311=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00339 in 1,613,780 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0039 ( 8 hom., cov: 32)
Exomes 𝑓: 0.0033 ( 54 hom. )
Consequence
CACNA2D3
NM_018398.3 synonymous
NM_018398.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.11
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
?
Variant 3-54581847-T-G is Benign according to our data. Variant chr3-54581847-T-G is described in ClinVar as [Benign]. Clinvar id is 3049724.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-4.11 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00333 (4866/1461518) while in subpopulation AMR AF= 0.0354 (1581/44678). AF 95% confidence interval is 0.0339. There are 54 homozygotes in gnomad4_exome. There are 2361 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 8 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA2D3 | NM_018398.3 | c.933T>G | p.Thr311= | synonymous_variant | 9/38 | ENST00000474759.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA2D3 | ENST00000474759.6 | c.933T>G | p.Thr311= | synonymous_variant | 9/38 | 1 | NM_018398.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00396 AC: 602AN: 152144Hom.: 8 Cov.: 32
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GnomAD3 exomes AF: 0.00830 AC: 2064AN: 248730Hom.: 39 AF XY: 0.00703 AC XY: 948AN XY: 134930
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GnomAD4 exome AF: 0.00333 AC: 4866AN: 1461518Hom.: 54 Cov.: 31 AF XY: 0.00325 AC XY: 2361AN XY: 727022
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GnomAD4 genome ? AF: 0.00395 AC: 601AN: 152262Hom.: 8 Cov.: 32 AF XY: 0.00462 AC XY: 344AN XY: 74460
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
CACNA2D3-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 13, 2021 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at