rs200076129
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_005866.4(SIGMAR1):c.463G>T(p.Gly155Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G155R) has been classified as Likely benign.
Frequency
Consequence
NM_005866.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIGMAR1 | NM_005866.4 | c.463G>T | p.Gly155Trp | missense_variant | 4/4 | ENST00000277010.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIGMAR1 | ENST00000277010.9 | c.463G>T | p.Gly155Trp | missense_variant | 4/4 | 1 | NM_005866.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152188Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000321 AC: 8AN: 248934Hom.: 0 AF XY: 0.0000297 AC XY: 4AN XY: 134780
GnomAD4 exome AF: 0.0000260 AC: 38AN: 1461732Hom.: 0 Cov.: 36 AF XY: 0.0000193 AC XY: 14AN XY: 727168
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152306Hom.: 0 Cov.: 31 AF XY: 0.0000403 AC XY: 3AN XY: 74470
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 30, 2019 | The p.G155W variant (also known as c.463G>T), located in coding exon 4 of the SIGMAR1 gene, results from a G to T substitution at nucleotide position 463. The glycine at codon 155 is replaced by tryptophan, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Autosomal recessive distal spinal muscular atrophy 2;C3280587:Amyotrophic lateral sclerosis type 16 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 155 of the SIGMAR1 protein (p.Gly155Trp). This variant is present in population databases (rs200076129, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SIGMAR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 843288). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at