3-63912684-GGCAGCAGCAGCAGCAGCAGCA-GGCAGCAGCAGCAGCA

Variant summary

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

The NM_001377405.1(ATXN7):​c.113_118delAGCAGC​(p.Gln38_Gln39del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00125 in 1,087,052 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 0.0015 ( 0 hom., cov: 23)
Exomes 𝑓: 0.0012 ( 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 GnomAd4 at 218 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ATXN7NM_001377405.1 linkuse as main transcriptc.113_118delAGCAGC p.Gln38_Gln39del disruptive_inframe_deletion 3/13 ENST00000674280.1 NP_001364334.1
ATXN7NM_001177387.1 linkuse as main transcriptc.113_118delAGCAGC p.Gln38_Gln39del disruptive_inframe_deletion 2/13 NP_001170858.1 O15265-2
ATXN7NM_000333.4 linkuse as main transcriptc.113_118delAGCAGC p.Gln38_Gln39del disruptive_inframe_deletion 3/13 NP_000324.1 O15265-1Q9UPD8
ATXN7NM_001377406.1 linkuse as main transcriptc.113_118delAGCAGC p.Gln38_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.113_118delAGCAGC p.Gln38_Gln39del disruptive_inframe_deletion 3/13 NM_001377405.1 ENSP00000501377.1 O15265-1

Frequencies

GnomAD3 genomes
AF:
0.00150
AC:
217
AN:
144616
Hom.:
0
Cov.:
23
show subpopulations
Gnomad AFR
AF:
0.00361
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000953
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:
0.000871
Gnomad OTH
AF:
0.000996
GnomAD4 exome
AF:
0.00121
AC:
1140
AN:
942334
Hom.:
0
AF XY:
0.00121
AC XY:
539
AN XY:
446524
show subpopulations
Gnomad4 AFR exome
AF:
0.00344
Gnomad4 AMR exome
AF:
0.000948
Gnomad4 ASJ exome
AF:
0.000119
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000150
Gnomad4 FIN exome
AF:
0.000637
Gnomad4 NFE exome
AF:
0.00123
Gnomad4 OTH exome
AF:
0.00118
GnomAD4 genome
AF:
0.00151
AC:
218
AN:
144718
Hom.:
0
Cov.:
23
AF XY:
0.00126
AC XY:
89
AN XY:
70412
show subpopulations
Gnomad4 AFR
AF:
0.00360
Gnomad4 AMR
AF:
0.000952
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000886
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