3-63912684-G-GGCAGCAGCA
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3BP6_ModerateBS1BS2
The NM_001377405.1(ATXN7):c.110_118dup(p.Gln37_Gln39dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.046 in 1,086,962 control chromosomes in the GnomAD database, including 796 homozygotes. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.034 ( 92 hom., cov: 23)
Exomes 𝑓: 0.048 ( 704 hom. )
Consequence
ATXN7
NM_001377405.1 inframe_insertion
NM_001377405.1 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.10
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 Benign. Variant got -11 ACMG points.
BP3
?
Nonframeshift variant in repetitive region in NM_001377405.1
BP6
?
Variant 3-63912684-G-GGCAGCAGCA is Benign according to our data. Variant chr3-63912684-G-GGCAGCAGCA is described in ClinVar as [Likely_benign]. Clinvar id is 3033271.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0342 (4953/144692) while in subpopulation NFE AF= 0.0483 (3159/65426). AF 95% confidence interval is 0.0469. There are 92 homozygotes in gnomad4. There are 2376 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
?
High AC in GnomAd at 4952 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATXN7 | NM_001377405.1 | c.110_118dup | p.Gln37_Gln39dup | inframe_insertion | 3/13 | ENST00000674280.1 | |
ATXN7 | NM_000333.4 | c.110_118dup | p.Gln37_Gln39dup | inframe_insertion | 3/13 | ||
ATXN7 | NM_001177387.1 | c.110_118dup | p.Gln37_Gln39dup | inframe_insertion | 2/13 | ||
ATXN7 | NM_001377406.1 | c.110_118dup | p.Gln37_Gln39dup | inframe_insertion | 2/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATXN7 | ENST00000674280.1 | c.110_118dup | p.Gln37_Gln39dup | inframe_insertion | 3/13 | NM_001377405.1 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0342 AC: 4952AN: 144590Hom.: 93 Cov.: 23
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GnomAD3 exomes AF: 0.0215 AC: 223AN: 10356Hom.: 4 AF XY: 0.0226 AC XY: 125AN XY: 5542
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GnomAD4 exome AF: 0.0478 AC: 45017AN: 942270Hom.: 704 Cov.: 26 AF XY: 0.0474 AC XY: 21160AN XY: 446526
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GnomAD4 genome ? AF: 0.0342 AC: 4953AN: 144692Hom.: 92 Cov.: 23 AF XY: 0.0338 AC XY: 2376AN XY: 70390
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
ATXN7-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 03, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at