GeneBe

rs193922929

Positions:

Variant summary

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

The NM_001377405.1(ATXN7):​c.98_118delAGCAGCAGCAGCAGCAGCAGC​(p.Gln33_Gln39del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000127 in 942,434 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: not found (cov: 23)
Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

ATXN7
NM_001377405.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.84
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 GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ATXN7NM_001377405.1 linkuse as main transcriptc.98_118delAGCAGCAGCAGCAGCAGCAGC p.Gln33_Gln39del disruptive_inframe_deletion 3/13 ENST00000674280.1 NP_001364334.1
ATXN7NM_001177387.1 linkuse as main transcriptc.98_118delAGCAGCAGCAGCAGCAGCAGC p.Gln33_Gln39del disruptive_inframe_deletion 2/13 NP_001170858.1 O15265-2
ATXN7NM_000333.4 linkuse as main transcriptc.98_118delAGCAGCAGCAGCAGCAGCAGC p.Gln33_Gln39del disruptive_inframe_deletion 3/13 NP_000324.1 O15265-1Q9UPD8
ATXN7NM_001377406.1 linkuse as main transcriptc.98_118delAGCAGCAGCAGCAGCAGCAGC p.Gln33_Gln39del disruptive_inframe_deletion 2/12 NP_001364335.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ATXN7ENST00000674280.1 linkuse as main transcriptc.98_118delAGCAGCAGCAGCAGCAGCAGC p.Gln33_Gln39del disruptive_inframe_deletion 3/13 NM_001377405.1 ENSP00000501377.1 O15265-1

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
AF:
0.0000127
AC:
12
AN:
942434
Hom.:
0
AF XY:
0.00000896
AC XY:
4
AN XY:
446588
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000145
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23
Bravo
AF:
0.0000151

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