NM_015046.7:c.7413A>T
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4
The NM_015046.7(SETX):c.7413A>T(p.Arg2471Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_015046.7 missense
Scores
Clinical Significance
Conservation
Publications
- amyotrophic lateral sclerosis type 4Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
- distal hereditary motor neuropathyInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
Genome browser will be placed here
ACMG classification
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SETX | ENST00000224140.6 | c.7413A>T | p.Arg2471Ser | missense_variant | Exon 26 of 26 | 1 | NM_015046.7 | ENSP00000224140.5 | ||
SETX | ENST00000436441.5 | c.2226A>T | p.Arg742Ser | missense_variant | Exon 17 of 17 | 5 | ENSP00000409143.1 | |||
SETX | ENST00000477049.1 | n.563A>T | non_coding_transcript_exon_variant | Exon 5 of 5 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152142Hom.: 0 Cov.: 32 show subpopulations
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461864Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727226 show subpopulations
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74326 show subpopulations
ClinVar
Submissions by phenotype
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2;C1865409:Amyotrophic lateral sclerosis type 4 Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with SETX-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with serine at codon 2471 of the SETX protein (p.Arg2471Ser). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and serine. -
not provided Uncertain:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at