3-63912714-A-AGCAGCAGCAGCAGCAGCAGCC
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3
The NM_001377405.1(ATXN7):c.118_119insAGCAGCAGCAGCAGCAGCCGC(p.Gln39_Pro40insGlnGlnGlnGlnGlnGlnPro) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000681 in 146,902 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000068 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
ATXN7
NM_001377405.1 disruptive_inframe_insertion
NM_001377405.1 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.825
Publications
3 publications found
Genes affected
ATXN7 (HGNC:10560): (ataxin 7) The autosomal dominant cerebellar ataxias (ADCA) are a heterogeneous group of neurodegenerative disorders characterized by progressive degeneration of the cerebellum, brain stem and spinal cord. Clinically, ADCA has been divided into three groups: ADCA types I-III. ADCAI is genetically heterogeneous, with five genetic loci, designated spinocerebellar ataxia (SCA) 1, 2, 3, 4 and 6, being assigned to five different chromosomes. ADCAII, which always presents with retinal degeneration (SCA7), and ADCAIII often referred to as the 'pure' cerebellar syndrome (SCA5), are most likely homogeneous disorders. Several SCA genes have been cloned and shown to contain CAG repeats in their coding regions. ADCA is caused by the expansion of the CAG repeats, producing an elongated polyglutamine tract in the corresponding protein. The expanded repeats are variable in size and unstable, usually increasing in size when transmitted to successive generations. This locus has been mapped to chromosome 3, and it has been determined that the diseased allele associated with spinocerebellar ataxia-7 contains 37-306 CAG repeats (near the N-terminus), compared to 4-35 in the normal allele. The encoded protein is a component of the SPT3/TAF9/GCN5 acetyltransferase (STAGA) and TBP-free TAF-containing (TFTC) chromatin remodeling complexes, and it thus plays a role in transcriptional regulation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]
ATXN7 Gene-Disease associations (from GenCC):
- spinocerebellar ataxia 7Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
- spinocerebellar ataxia type 7Inheritance: AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
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_001377405.1
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001377405.1. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ATXN7 | NM_001377405.1 | MANE Select | c.118_119insAGCAGCAGCAGCAGCAGCCGC | p.Gln39_Pro40insGlnGlnGlnGlnGlnGlnPro | disruptive_inframe_insertion | Exon 3 of 13 | NP_001364334.1 | O15265-1 | |
| ATXN7 | NM_001177387.1 | c.118_119insAGCAGCAGCAGCAGCAGCCGC | p.Gln39_Pro40insGlnGlnGlnGlnGlnGlnPro | disruptive_inframe_insertion | Exon 2 of 13 | NP_001170858.1 | O15265-2 | ||
| ATXN7 | NM_000333.4 | c.118_119insAGCAGCAGCAGCAGCAGCCGC | p.Gln39_Pro40insGlnGlnGlnGlnGlnGlnPro | disruptive_inframe_insertion | Exon 3 of 13 | NP_000324.1 | O15265-1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ATXN7 | ENST00000674280.1 | MANE Select | c.118_119insAGCAGCAGCAGCAGCAGCCGC | p.Gln39_Pro40insGlnGlnGlnGlnGlnGlnPro | disruptive_inframe_insertion | Exon 3 of 13 | ENSP00000501377.1 | O15265-1 | |
| ATXN7 | ENST00000295900.10 | TSL:1 | c.118_119insAGCAGCAGCAGCAGCAGCCGC | p.Gln39_Pro40insGlnGlnGlnGlnGlnGlnPro | disruptive_inframe_insertion | Exon 3 of 13 | ENSP00000295900.6 | O15265-1 | |
| ATXN7 | ENST00000522345.2 | TSL:2 | c.118_119insAGCAGCAGCAGCAGCAGCCGC | p.Gln39_Pro40insGlnGlnGlnGlnGlnGlnPro | disruptive_inframe_insertion | Exon 1 of 12 | ENSP00000428067.2 | O15265-2 |
Frequencies
GnomAD3 genomes 0.00000681 AC: 1AN: 146902Hom.: 0 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
146902
Hom.:
Cov.:
31
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: 0.00000751 AC: 8AN: 1065666Hom.: 0 Cov.: 32 AF XY: 0.00000783 AC XY: 4AN XY: 510618 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
8
AN:
1065666
Hom.:
Cov.:
32
AF XY:
AC XY:
4
AN XY:
510618
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
2
AN:
20934
American (AMR)
AF:
AC:
0
AN:
11452
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
13278
East Asian (EAS)
AF:
AC:
2
AN:
19748
South Asian (SAS)
AF:
AC:
0
AN:
25970
European-Finnish (FIN)
AF:
AC:
0
AN:
31604
Middle Eastern (MID)
AF:
AC:
0
AN:
2714
European-Non Finnish (NFE)
AF:
AC:
4
AN:
899676
Other (OTH)
AF:
AC:
0
AN:
40290
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.287
Heterozygous variant carriers
0
1
2
3
4
5
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
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>80
Age
GnomAD4 genome 0.00000681 AC: 1AN: 146902Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 71430 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
146902
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
71430
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
40312
American (AMR)
AF:
AC:
0
AN:
14866
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3390
East Asian (EAS)
AF:
AC:
0
AN:
4822
South Asian (SAS)
AF:
AC:
0
AN:
4766
European-Finnish (FIN)
AF:
AC:
0
AN:
9136
Middle Eastern (MID)
AF:
AC:
0
AN:
310
European-Non Finnish (NFE)
AF:
AC:
1
AN:
66366
Other (OTH)
AF:
AC:
0
AN:
2026
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
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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