GeneBe

rs193922928

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_004993.6(ATXN3):​c.904_915delCAGCAGCAGCAG​(p.Gln302_Gln305del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000761 in 1,314,560 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 DEL_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: not found (cov: 20)
Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

ATXN3
NM_004993.6 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.37

Publications

0 publications found
Variant links:
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 disease
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae)
  • Machado-Joseph disease type 1
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Machado-Joseph disease type 2
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • Machado-Joseph disease type 3
    Inheritance: 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
ATXN3NM_004993.6 linkc.904_915delCAGCAGCAGCAG p.Gln302_Gln305del conservative_inframe_deletion Exon 10 of 11 ENST00000644486.2 NP_004984.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATXN3ENST00000644486.2 linkc.904_915delCAGCAGCAGCAG p.Gln302_Gln305del conservative_inframe_deletion Exon 10 of 11 NM_004993.6 ENSP00000496695.1

Frequencies

GnomAD3 genomes
Cov.:
20
GnomAD4 exome
AF:
7.61e-7
AC:
1
AN:
1314560
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
657302
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
27564
American (AMR)
AF:
0.00
AC:
0
AN:
40510
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
24398
East Asian (EAS)
AF:
0.0000267
AC:
1
AN:
37452
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79494
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48912
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5148
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
995974
Other (OTH)
AF:
0.00
AC:
0
AN:
55108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
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
Cov.:
20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
2.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs193922928; hg19: chr14-92537354; API