3-63912684-GGCAGCAGCAGCAGCAGCAGCA-GGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCA

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3BS2

The NM_001377405.1(ATXN7):​c.98_118dupAGCAGCAGCAGCAGCAGCAGC​(p.Gln33_Gln39dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.00022 in 1,087,142 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 23)
Exomes 𝑓: 0.00017 ( 1 hom. )

Consequence

ATXN7
NM_001377405.1 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.10
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP3
Nonframeshift variant in repetitive region in NM_001377405.1
BS2
High AC in GnomAd4 at 78 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ATXN7NM_001377405.1 linkc.98_118dupAGCAGCAGCAGCAGCAGCAGC p.Gln33_Gln39dup disruptive_inframe_insertion 3/13 ENST00000674280.1 NP_001364334.1
ATXN7NM_001177387.1 linkc.98_118dupAGCAGCAGCAGCAGCAGCAGC p.Gln33_Gln39dup disruptive_inframe_insertion 2/13 NP_001170858.1 O15265-2
ATXN7NM_000333.4 linkc.98_118dupAGCAGCAGCAGCAGCAGCAGC p.Gln33_Gln39dup disruptive_inframe_insertion 3/13 NP_000324.1 O15265-1Q9UPD8
ATXN7NM_001377406.1 linkc.98_118dupAGCAGCAGCAGCAGCAGCAGC p.Gln33_Gln39dup disruptive_inframe_insertion 2/12 NP_001364335.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ATXN7ENST00000674280.1 linkc.98_118dupAGCAGCAGCAGCAGCAGCAGC p.Gln33_Gln39dup disruptive_inframe_insertion 3/13 NM_001377405.1 ENSP00000501377.1 O15265-1

Frequencies

GnomAD3 genomes
AF:
0.000532
AC:
77
AN:
144614
Hom.:
0
Cov.:
23
show subpopulations
Gnomad AFR
AF:
0.00170
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000136
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:
0.0000764
Gnomad OTH
AF:
0.000996
GnomAD4 exome
AF:
0.000171
AC:
161
AN:
942426
Hom.:
1
Cov.:
26
AF XY:
0.000166
AC XY:
74
AN XY:
446584
show subpopulations
Gnomad4 AFR exome
AF:
0.00237
Gnomad4 AMR exome
AF:
0.000189
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000250
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000127
Gnomad4 OTH exome
AF:
0.000242
GnomAD4 genome
AF:
0.000539
AC:
78
AN:
144716
Hom.:
0
Cov.:
23
AF XY:
0.000497
AC XY:
35
AN XY:
70410
show subpopulations
Gnomad4 AFR
AF:
0.00173
Gnomad4 AMR
AF:
0.000136
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000764
Gnomad4 OTH
AF:
0.000985

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: rs193922929; hg19: chr3-63898360; API