rs201317659
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_015046.7(SETX):c.5375-12_5375-10del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,610,992 control chromosomes in the GnomAD database, including 21 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0054 ( 15 hom., cov: 32)
Exomes 𝑓: 0.00067 ( 6 hom. )
Consequence
SETX
NM_015046.7 splice_polypyrimidine_tract, intron
NM_015046.7 splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.10
Genes affected
SETX (HGNC:445): (senataxin) This gene encodes a protein named for its homology to the Sen1p protein of fungi which has RNA helicase activity encoded by a domain at the C-terminal end of the protein. The protein encoded by this gene contains a DNA/RNA helicase domain at its C-terminal end which suggests that it may be involved in both DNA and RNA processing. Mutations in this gene have been associated with ataxia-ocular apraxia-2 (AOA2) and an autosomal dominant form of juvenile amyotrophic lateral sclerosis (ALS4). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 9-132300812-CAAG-C is Benign according to our data. Variant chr9-132300812-CAAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 468517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-132300812-CAAG-C is described in Lovd as [Likely_benign]. Variant chr9-132300812-CAAG-C is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00543 (826/152082) while in subpopulation AFR AF= 0.0185 (766/41512). AF 95% confidence interval is 0.0174. There are 15 homozygotes in gnomad4. There are 413 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 15 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SETX | NM_015046.7 | c.5375-12_5375-10del | splice_polypyrimidine_tract_variant, intron_variant | ENST00000224140.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SETX | ENST00000224140.6 | c.5375-12_5375-10del | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_015046.7 | P1 | |||
SETX | ENST00000436441.5 | c.101-12_101-10del | splice_polypyrimidine_tract_variant, intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00541 AC: 822AN: 151964Hom.: 15 Cov.: 32
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GnomAD3 exomes AF: 0.00153 AC: 380AN: 248510Hom.: 5 AF XY: 0.00124 AC XY: 167AN XY: 134570
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GnomAD4 exome AF: 0.000668 AC: 974AN: 1458910Hom.: 6 AF XY: 0.000606 AC XY: 440AN XY: 725878
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GnomAD4 genome ? AF: 0.00543 AC: 826AN: 152082Hom.: 15 Cov.: 32 AF XY: 0.00556 AC XY: 413AN XY: 74330
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:10
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 25, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 13, 2020 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 29, 2020 | - - |
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2;C1865409:Amyotrophic lateral sclerosis type 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Amyotrophic lateral sclerosis type 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
Hereditary spastic paraplegia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Aug 01, 2019 | - - |
SETX-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 20, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at