3-53730470-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PP3_ModerateBS1_Supporting
The NM_000720.4(CACNA1D):c.2310C>A(p.Ile770=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000333 in 1,613,408 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. I770I) has been classified as Likely benign.
Frequency
Consequence
NM_000720.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CACNA1D | NM_000720.4 | c.2310C>A | p.Ile770= | synonymous_variant | 17/49 | ENST00000288139.11 | |
CACNA1D | NM_001128840.3 | c.2250C>A | p.Ile750= | synonymous_variant | 16/48 | ENST00000350061.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CACNA1D | ENST00000288139.11 | c.2310C>A | p.Ile770= | synonymous_variant | 17/49 | 1 | NM_000720.4 | P2 | |
CACNA1D | ENST00000350061.11 | c.2250C>A | p.Ile750= | synonymous_variant | 16/48 | 1 | NM_001128840.3 |
Frequencies
GnomAD3 genomes AF: 0.000348 AC: 53AN: 152188Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000294 AC: 74AN: 251448Hom.: 0 AF XY: 0.000243 AC XY: 33AN XY: 135918
GnomAD4 exome AF: 0.000331 AC: 484AN: 1461102Hom.: 0 Cov.: 31 AF XY: 0.000310 AC XY: 225AN XY: 726930
GnomAD4 genome AF: 0.000348 AC: 53AN: 152306Hom.: 0 Cov.: 33 AF XY: 0.000322 AC XY: 24AN XY: 74458
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 26, 2023 | In silico analysis supports a deleterious effect on splicing; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 30847666) - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2022 | CACNA1D: PP3 - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 10, 2017 | The p.Ile770Ile variant in CACNA1D has not been previously reported in individua ls with hearing loss or SANDD syndrome, but has been identified in 0.06% (20/344 20) of Latino chromosomes and 0.04% (53/126716) European chromosomes by the Geno me Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs41276 445). Although this variant has been seen in the general population, its frequen cy is not high enough to rule out a pathogenic role. Computational tools suggest that this variant may create a new 3' splicing site, though this information is not predictive enough to determine pathogenicity. In summary, the clinical sign ificance of the p.Ile770Ile variant is uncertain. - |
Sinoatrial node dysfunction and deafness Uncertain:1
Uncertain significance, no assertion criteria provided | research | Division of Human Genetics, Children's Hospital of Philadelphia | Oct 30, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at