rs150673589
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_015046.7(SETX):c.7114G>A(p.Asp2372Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00191 in 1,613,594 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0025 ( 5 hom., cov: 32)
Exomes 𝑓: 0.0018 ( 32 hom. )
Consequence
SETX
NM_015046.7 missense
NM_015046.7 missense
Scores
2
6
8
Clinical Significance
Conservation
PhyloP100: 5.83
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.011762232).
BP6
?
Variant 9-132271795-C-T is Benign according to our data. Variant chr9-132271795-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-132271795-C-T is described in Lovd as [Likely_benign]. Variant chr9-132271795-C-T is described in Lovd as [Likely_pathogenic].
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00248 (377/152272) while in subpopulation EAS AF= 0.021 (109/5188). AF 95% confidence interval is 0.0178. There are 5 homozygotes in gnomad4. There are 197 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 5 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SETX | NM_015046.7 | c.7114G>A | p.Asp2372Asn | missense_variant | 24/26 | ENST00000224140.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SETX | ENST00000224140.6 | c.7114G>A | p.Asp2372Asn | missense_variant | 24/26 | 1 | NM_015046.7 | P1 | |
SETX | ENST00000436441.5 | c.1840G>A | p.Asp614Asn | missense_variant | 14/17 | 5 | |||
SETX | ENST00000477049.1 | n.141G>A | non_coding_transcript_exon_variant | 2/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00244 AC: 371AN: 152154Hom.: 5 Cov.: 32
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GnomAD3 exomes AF: 0.00609 AC: 1532AN: 251444Hom.: 22 AF XY: 0.00521 AC XY: 708AN XY: 135896
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GnomAD4 exome AF: 0.00185 AC: 2700AN: 1461322Hom.: 32 Cov.: 30 AF XY: 0.00181 AC XY: 1316AN XY: 727000
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GnomAD4 genome ? AF: 0.00248 AC: 377AN: 152272Hom.: 5 Cov.: 32 AF XY: 0.00265 AC XY: 197AN XY: 74456
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Asia WGS
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:15
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:7
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | SETX: BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 21, 2021 | This variant is associated with the following publications: (PMID: 30076350, 25382069, 25174650) - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 08, 2021 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 21, 2020 | - - |
Amyotrophic lateral sclerosis type 4 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
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 29, 2024 | - - |
Hereditary spastic paraplegia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jul 01, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;T
Sift4G
Benign
T;D
Polyphen
1.0
.;D
Vest4
0.51
MVP
MPC
0.42
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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