chr9-132330130-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_015046.7(SETX):c.1468G>A(p.Val490Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000279 in 1,612,566 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_015046.7 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152262Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 250872Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135580
GnomAD4 exome AF: 0.0000260 AC: 38AN: 1460304Hom.: 0 Cov.: 35 AF XY: 0.0000248 AC XY: 18AN XY: 726124
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152262Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74388
ClinVar
Submissions by phenotype
not provided Uncertain:3
- -
Reported previously as a variant of uncertain significance in a patient with axonal nerve conduction study findings, ataxia, dysarthria, and nystagmus; however, no segregation information was provided (Hartley et al., 2018); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28708278) -
- -
Inborn genetic diseases Uncertain:1
The p.V490I variant (also known as c.1468G>A), located in coding exon 8 of the SETX gene, results from a G to A substitution at nucleotide position 1468. The valine at codon 490 is replaced by isoleucine, an amino acid with highly similar properties. This variant was detected in an individual with hereditary sensory neuropathy; however, clinical details were limited (Hartley T et al. Clin Genet, 2018 02;93:301-309). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the supporting evidence, this variant is unlikely to be causative of amyotrophic lateral sclerosis 4 (ALS4); however, its contribution to the development of spinocerebellar ataxia with axonal neuropathy 2 (SCAN2) is uncertain. -
Amyotrophic lateral sclerosis type 4 Uncertain:1
- -
Spastic ataxia Uncertain:1
- -
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 Uncertain:1
- -
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2;C1865409:Amyotrophic lateral sclerosis type 4 Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at