rs763461489
Variant names:
Your query was ambiguous. Multiple possible variants found:
- chr14-92071009-C-CA
- chr14-92071009-C-CACTGCTGCTGCTGCTGCTGCT
- chr14-92071009-C-CG
- chr14-92071009-C-CGCT
- chr14-92071009-C-CGCTGCT
- chr14-92071009-C-CGCTGCTGCT
- chr14-92071009-C-CGCTGCTGCTGCT
- chr14-92071009-C-CGCTGCTGCTGCTGCT
- chr14-92071009-C-CGCTGCTGCTGCTGCTG
- chr14-92071009-C-CGCTGCTGCTGCTGCTGCT
- chr14-92071009-C-CGCTGCTGCTGCTGCTGCTGCT
- chr14-92071009-C-CGCTGCTGCTGCTGCTGCTGCTGCT
- chr14-92071009-C-CGCTGCTGCTGCTGCTGCTGCTGCTGCT
- chr14-92071009-C-CGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT
- chr14-92071009-C-CGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT
- chr14-92071009-C-CGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT
- chr14-92071009-C-CGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT
- chr14-92071009-C-CGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCT
- chr14-92071009-C-CT
- chr14-92071009-C-CTCTGCTGCTGCTGCTGCTGCTGCT
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2
The NM_004993.6(ATXN3):c.916_917insT(p.Gly306ValfsTer12) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000907 in 66,138 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G306G) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000091 ( 0 hom., cov: 22)
Exomes 𝑓: 0.0000038 ( 1 hom. )
Failed GnomAD Quality Control
Consequence
ATXN3
NM_004993.6 frameshift
NM_004993.6 frameshift
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.802
Publications
6 publications found
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]
ATXN3 Gene-Disease associations (from GenCC):
- Machado-Joseph diseaseInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
- Machado-Joseph disease type 1Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Machado-Joseph disease type 2Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- Machado-Joseph disease type 3Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -4 ACMG points.
BS2
High AC in GnomAd4 at 6 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| ATXN3 | NM_004993.6 | c.916_917insT | p.Gly306ValfsTer12 | frameshift_variant | Exon 10 of 11 | ENST00000644486.2 | NP_004984.2 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| ATXN3 | ENST00000644486.2 | c.916_917insT | p.Gly306ValfsTer12 | frameshift_variant | Exon 10 of 11 | NM_004993.6 | ENSP00000496695.1 |
Frequencies
GnomAD3 genomes 0.0000907 AC: 6AN: 66138Hom.: 0 Cov.: 22 show subpopulations
GnomAD3 genomes
AF:
AC:
6
AN:
66138
Hom.:
Cov.:
22
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000385 AC: 3AN: 779474Hom.: 1 Cov.: 50 AF XY: 0.00000508 AC XY: 2AN XY: 393814 show subpopulations
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
3
AN:
779474
Hom.:
Cov.:
50
AF XY:
AC XY:
2
AN XY:
393814
show subpopulations
African (AFR)
AF:
AC:
1
AN:
12078
American (AMR)
AF:
AC:
0
AN:
19378
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
15484
East Asian (EAS)
AF:
AC:
0
AN:
34114
South Asian (SAS)
AF:
AC:
2
AN:
50442
European-Finnish (FIN)
AF:
AC:
0
AN:
32034
Middle Eastern (MID)
AF:
AC:
0
AN:
2870
European-Non Finnish (NFE)
AF:
AC:
0
AN:
580748
Other (OTH)
AF:
AC:
0
AN:
32326
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.0000907 AC: 6AN: 66138Hom.: 0 Cov.: 22 AF XY: 0.0000928 AC XY: 3AN XY: 32332 show subpopulations
GnomAD4 genome
AF:
AC:
6
AN:
66138
Hom.:
Cov.:
22
AF XY:
AC XY:
3
AN XY:
32332
show subpopulations
African (AFR)
AF:
AC:
6
AN:
11678
American (AMR)
AF:
AC:
0
AN:
5492
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2032
East Asian (EAS)
AF:
AC:
0
AN:
4394
South Asian (SAS)
AF:
AC:
0
AN:
2692
European-Finnish (FIN)
AF:
AC:
0
AN:
5324
Middle Eastern (MID)
AF:
AC:
0
AN:
168
European-Non Finnish (NFE)
AF:
AC:
0
AN:
33000
Other (OTH)
AF:
AC:
0
AN:
916
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.508
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.