chr3-63912684-G-GGCA
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP3BA1
The NM_001377405.1(ATXN7):c.116_118dupAGC(p.Gln39dup) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.0327 in 1,083,874 control chromosomes in the GnomAD database, including 941 homozygotes. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: 𝑓 0.063 ( 544 hom., cov: 23)
Exomes 𝑓: 0.028 ( 397 hom. )
Consequence
ATXN7
NM_001377405.1 disruptive_inframe_insertion
NM_001377405.1 disruptive_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 -9 ACMG points.
BP3
Nonframeshift variant in repetitive region in NM_001377405.1
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ATXN7 | NM_001377405.1 | c.116_118dupAGC | p.Gln39dup | disruptive_inframe_insertion | 3/13 | ENST00000674280.1 | NP_001364334.1 | |
ATXN7 | NM_001177387.1 | c.116_118dupAGC | p.Gln39dup | disruptive_inframe_insertion | 2/13 | NP_001170858.1 | ||
ATXN7 | NM_000333.4 | c.116_118dupAGC | p.Gln39dup | disruptive_inframe_insertion | 3/13 | NP_000324.1 | ||
ATXN7 | NM_001377406.1 | c.116_118dupAGC | p.Gln39dup | disruptive_inframe_insertion | 2/12 | NP_001364335.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ATXN7 | ENST00000674280.1 | c.116_118dupAGC | p.Gln39dup | disruptive_inframe_insertion | 3/13 | NM_001377405.1 | ENSP00000501377.1 |
Frequencies
GnomAD3 genomes AF: 0.0625 AC: 9030AN: 144576Hom.: 542 Cov.: 23
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GnomAD3 exomes AF: 0.0267 AC: 277AN: 10356Hom.: 8 AF XY: 0.0281 AC XY: 156AN XY: 5542
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GnomAD4 exome AF: 0.0281 AC: 26375AN: 939196Hom.: 397 Cov.: 26 AF XY: 0.0276 AC XY: 12298AN XY: 445070
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GnomAD4 genome AF: 0.0626 AC: 9057AN: 144678Hom.: 544 Cov.: 23 AF XY: 0.0614 AC XY: 4323AN XY: 70392
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Retinal dystrophy Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg | Jan 01, 2022 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at