rs12896583
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_004993.6(ATXN3):c.891A>G(p.Gln297=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.034 ( 2 hom., cov: 0)
Exomes 𝑓: 0.19 ( 273 hom. )
Failed GnomAD Quality Control
Consequence
ATXN3
NM_004993.6 synonymous
NM_004993.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.273
Genes affected
ATXN3 (HGNC:7106): (ataxin 3) Machado-Joseph disease, also known as spinocerebellar ataxia-3, is an autosomal dominant neurologic disorder. The protein encoded by this gene contains (CAG)n repeats in the coding region, and the expansion of these repeats from the normal 12-44 to 52-86 is one cause of Machado-Joseph disease. There is a negative correlation between the age of onset and CAG repeat numbers. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 14-92071035-T-C is Benign according to our data. Variant chr14-92071035-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 128514.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-92071035-T-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.273 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATXN3 | NM_004993.6 | c.891A>G | p.Gln297= | synonymous_variant | 10/11 | ENST00000644486.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATXN3 | ENST00000644486.2 | c.891A>G | p.Gln297= | synonymous_variant | 10/11 | NM_004993.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 686AN: 20002Hom.: 2 Cov.: 0 FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.188 AC: 94896AN: 503886Hom.: 273 Cov.: 47 AF XY: 0.180 AC XY: 45777AN XY: 254024
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.0344 AC: 689AN: 20016Hom.: 2 Cov.: 0 AF XY: 0.0358 AC XY: 365AN XY: 10184
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Data not reliable, filtered out with message: AS_VQSR
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 12, 2014 | - - |
ATXN3-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 31, 2019 | 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). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 21, 2019 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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