rs3739922
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_015046.7(SETX):āc.3455T>Gā(p.Phe1152Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0455 in 1,613,922 control chromosomes in the GnomAD database, including 2,842 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F1152L) has been classified as Uncertain significance.
Frequency
Consequence
NM_015046.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SETX | NM_015046.7 | c.3455T>G | p.Phe1152Cys | missense_variant | 10/26 | ENST00000224140.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SETX | ENST00000224140.6 | c.3455T>G | p.Phe1152Cys | missense_variant | 10/26 | 1 | NM_015046.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0500 AC: 7611AN: 152068Hom.: 319 Cov.: 32
GnomAD3 exomes AF: 0.0652 AC: 16354AN: 250992Hom.: 997 AF XY: 0.0633 AC XY: 8585AN XY: 135644
GnomAD4 exome AF: 0.0451 AC: 65868AN: 1461736Hom.: 2524 Cov.: 37 AF XY: 0.0456 AC XY: 33123AN XY: 727158
GnomAD4 genome ? AF: 0.0500 AC: 7615AN: 152186Hom.: 318 Cov.: 32 AF XY: 0.0514 AC XY: 3824AN XY: 74406
ClinVar
Submissions by phenotype
not specified Benign:8
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 14, 2012 | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
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:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 11, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Amyotrophic lateral sclerosis type 4 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
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. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 17, 2018 | This variant is associated with the following publications: (PMID: 24694197) - |
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at