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, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
  • 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

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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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004993.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ATXN3
NM_004993.6
MANE Select
c.904_915delCAGCAGCAGCAGp.Gln302_Gln305del
conservative_inframe_deletion
Exon 10 of 11NP_004984.2
ATXN3
NM_001127696.2
c.859_870delCAGCAGCAGCAGp.Gln287_Gln290del
conservative_inframe_deletion
Exon 9 of 10NP_001121168.1P54252-4
ATXN3
NM_001127697.3
c.751_762delCAGCAGCAGCAGp.Gln251_Gln254del
conservative_inframe_deletion
Exon 8 of 9NP_001121169.2A0A0A0MS38

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ATXN3
ENST00000644486.2
MANE Select
c.904_915delCAGCAGCAGCAGp.Gln302_Gln305del
conservative_inframe_deletion
Exon 10 of 11ENSP00000496695.1P54252-2
ATXN3
ENST00000532032.5
TSL:1
c.904_915delCAGCAGCAGCAGp.Gln302_Gln305del
conservative_inframe_deletion
Exon 10 of 10ENSP00000437157.1P54252-1
ATXN3
ENST00000503767.5
TSL:1
c.859_870delCAGCAGCAGCAGp.Gln287_Gln290del
conservative_inframe_deletion
Exon 9 of 10ENSP00000426697.1P54252-4

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 v4.9

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