rs140147684
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_015046.7(SETX):āc.4096T>Cā(p.Ser1366Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000388 in 1,614,016 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_015046.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SETX | NM_015046.7 | c.4096T>C | p.Ser1366Pro | missense_variant | 10/26 | ENST00000224140.6 | NP_055861.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SETX | ENST00000224140.6 | c.4096T>C | p.Ser1366Pro | missense_variant | 10/26 | 1 | NM_015046.7 | ENSP00000224140 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000269 AC: 41AN: 152246Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000247 AC: 62AN: 251310Hom.: 1 AF XY: 0.000206 AC XY: 28AN XY: 135836
GnomAD4 exome AF: 0.000401 AC: 586AN: 1461770Hom.: 1 Cov.: 65 AF XY: 0.000399 AC XY: 290AN XY: 727188
GnomAD4 genome AF: 0.000269 AC: 41AN: 152246Hom.: 0 Cov.: 32 AF XY: 0.000336 AC XY: 25AN XY: 74382
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:5
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Apr 07, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jan 21, 2020 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | SETX: BP4 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 12, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 25, 2022 | The p.S1366P variant (also known as c.4096T>C), located in coding exon 8 of the SETX gene, results from a T to C substitution at nucleotide position 4096. The serine at codon 1366 is replaced by proline, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the supporting evidence, this variant is unlikely to be causative of autosomal dominant juvenile amyotrophic lateral sclerosis 4 (ALS4); however, its contribution to the development of autosomal recessive spinocerebellar ataxia with axonal neuropathy 2 (SCAN2) is uncertain. - |
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2;C1865409:Amyotrophic lateral sclerosis type 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 23, 2023 | - - |
Amyotrophic lateral sclerosis type 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
SETX-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 31, 2022 | 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at