14-92071010-CCTGCTGCTGCTG-CCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTG
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3
The NM_004993.6(ATXN3):c.915_916insCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG(p.Gln305_Gly306insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000070 ( 0 hom., cov: 20)
Exomes 𝑓: 0.0000023 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ATXN3
NM_004993.6 conservative_inframe_insertion
NM_004993.6 conservative_inframe_insertion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.168
Publications
1 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 -1 ACMG points.
BP3
Nonframeshift variant in repetitive region in NM_004993.6
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| ATXN3 | NM_004993.6 | c.915_916insCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG | p.Gln305_Gly306insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln | conservative_inframe_insertion | 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.915_916insCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAG | p.Gln305_Gly306insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln | conservative_inframe_insertion | Exon 10 of 11 | NM_004993.6 | ENSP00000496695.1 |
Frequencies
GnomAD3 genomes 0.00000702 AC: 1AN: 142396Hom.: 0 Cov.: 20 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
142396
Hom.:
Cov.:
20
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: 0.00000228 AC: 3AN: 1314558Hom.: 0 Cov.: 92 AF XY: 0.00000304 AC XY: 2AN XY: 657300 show subpopulations
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
3
AN:
1314558
Hom.:
Cov.:
92
AF XY:
AC XY:
2
AN XY:
657300
show subpopulations
African (AFR)
AF:
AC:
1
AN:
27564
American (AMR)
AF:
AC:
0
AN:
40510
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24398
East Asian (EAS)
AF:
AC:
0
AN:
37452
South Asian (SAS)
AF:
AC:
0
AN:
79494
European-Finnish (FIN)
AF:
AC:
0
AN:
48912
Middle Eastern (MID)
AF:
AC:
0
AN:
5148
European-Non Finnish (NFE)
AF:
AC:
1
AN:
995972
Other (OTH)
AF:
AC:
1
AN:
55108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.442
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000702 AC: 1AN: 142396Hom.: 0 Cov.: 20 AF XY: 0.0000145 AC XY: 1AN XY: 69104 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
142396
Hom.:
Cov.:
20
AF XY:
AC XY:
1
AN XY:
69104
show subpopulations
African (AFR)
AF:
AC:
1
AN:
36200
American (AMR)
AF:
AC:
0
AN:
14398
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3412
East Asian (EAS)
AF:
AC:
0
AN:
4642
South Asian (SAS)
AF:
AC:
0
AN:
4314
European-Finnish (FIN)
AF:
AC:
0
AN:
9884
Middle Eastern (MID)
AF:
AC:
0
AN:
304
European-Non Finnish (NFE)
AF:
AC:
0
AN:
66422
Other (OTH)
AF:
AC:
0
AN:
1940
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
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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