GeneBe

rs193922928

Positions:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_004993.6(ATXN3):​c.910_915del​(p.Gln304_Gln305del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000206 in 1,456,940 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000056 ( 0 hom., cov: 20)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ATXN3
NM_004993.6 inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.37
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ATXN3NM_004993.6 linkuse as main transcriptc.910_915del p.Gln304_Gln305del inframe_deletion 10/11 ENST00000644486.2 NP_004984.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ATXN3ENST00000644486.2 linkuse as main transcriptc.910_915del p.Gln304_Gln305del inframe_deletion 10/11 NM_004993.6 ENSP00000496695 P1P54252-2

Frequencies

GnomAD3 genomes
AF:
0.0000562
AC:
8
AN:
142396
Hom.:
0
Cov.:
20
show subpopulations
Gnomad AFR
AF:
0.000110
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000695
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000452
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000167
AC:
22
AN:
1314544
Hom.:
0
AF XY:
0.0000122
AC XY:
8
AN XY:
657294
show subpopulations
Gnomad4 AFR exome
AF:
0.000254
Gnomad4 AMR exome
AF:
0.0000987
Gnomad4 ASJ exome
AF:
0.0000410
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000126
Gnomad4 FIN exome
AF:
0.0000204
Gnomad4 NFE exome
AF:
0.00000803
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000562
AC:
8
AN:
142396
Hom.:
0
Cov.:
20
AF XY:
0.0000434
AC XY:
3
AN XY:
69104
show subpopulations
Gnomad4 AFR
AF:
0.000110
Gnomad4 AMR
AF:
0.0000695
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000452
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000491

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs193922928; hg19: chr14-92537354; API