rs12352982
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_015046.7(SETX):c.3182C>T(p.Pro1061Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00267 in 1,613,740 control chromosomes in the GnomAD database, including 110 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1061A) has been classified as Likely benign.
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.3182C>T | p.Pro1061Leu | missense_variant | 10/26 | ENST00000224140.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SETX | ENST00000224140.6 | c.3182C>T | p.Pro1061Leu | missense_variant | 10/26 | 1 | NM_015046.7 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0145 AC: 2203AN: 152012Hom.: 52 Cov.: 32
GnomAD3 exomes AF: 0.00372 AC: 934AN: 251072Hom.: 20 AF XY: 0.00273 AC XY: 370AN XY: 135736
GnomAD4 exome AF: 0.00143 AC: 2092AN: 1461610Hom.: 53 Cov.: 37 AF XY: 0.00128 AC XY: 933AN XY: 727114
GnomAD4 genome AF: 0.0146 AC: 2219AN: 152130Hom.: 57 Cov.: 32 AF XY: 0.0143 AC XY: 1065AN XY: 74388
ClinVar
Submissions by phenotype
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 22, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 05, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 13, 2017 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
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. - |
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. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic 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 29, 2024 | - - |
Hereditary spastic paraplegia Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | May 14, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at