chr21-31663829-G-C
Variant summary
Our verdict is Pathogenic. Variant got 24 ACMG points: 24P and 0B. PS1_Very_StrongPM1PM2PP3_StrongPP5_Very_Strong
The NM_000454.5(SOD1):c.112G>C(p.Gly38Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Pathogenicin ClinVar.
Frequency
Consequence
NM_000454.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 24 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOD1 | NM_000454.5 | c.112G>C | p.Gly38Arg | missense_variant | 2/5 | ENST00000270142.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOD1 | ENST00000270142.11 | c.112G>C | p.Gly38Arg | missense_variant | 2/5 | 1 | NM_000454.5 | P1 | |
SOD1 | ENST00000389995.4 | c.55G>C | p.Gly19Arg | missense_variant | 2/5 | 3 | |||
SOD1 | ENST00000470944.1 | n.1040G>C | non_coding_transcript_exon_variant | 2/5 | 2 | ||||
SOD1 | ENST00000476106.5 | n.375G>C | non_coding_transcript_exon_variant | 3/5 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Amyotrophic lateral sclerosis type 1 Pathogenic:3
Pathogenic, criteria provided, single submitter | research | Suna and Inan Kirac Foundation Neurodegeneration Research Laboratory, Koc University | Mar 31, 2020 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Institute of Human Genetics, Cologne University | Apr 25, 2018 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 25, 2021 | This variant is also known as p.Gly37Arg. For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SOD1 protein function. ClinVar contains an entry for this variant (Variation ID: 549678). This missense change has been observed in individuals with amyotrophic lateral sclerosis (PMID: 16674979, 31788332). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 38 of the SOD1 protein (p.Gly38Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at