21-31659786-T-C
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_000454.5(SOD1):c.17T>C(p.Val6Ala) variant causes a missense change. 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 Uncertain significance (★).
Frequency
Consequence
NM_000454.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SOD1 | ENST00000270142.11 | c.17T>C | p.Val6Ala | missense_variant | Exon 1 of 5 | 1 | NM_000454.5 | ENSP00000270142.7 | ||
SOD1 | ENST00000389995.4 | c.15+2T>C | splice_donor_variant, intron_variant | Intron 1 of 4 | 3 | ENSP00000374645.4 | ||||
SOD1 | ENST00000470944.1 | n.78T>C | non_coding_transcript_exon_variant | Exon 1 of 5 | 2 | |||||
SOD1 | ENST00000476106.5 | n.94T>C | non_coding_transcript_exon_variant | Exon 1 of 5 | 5 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Amyotrophic lateral sclerosis type 1 Uncertain:1
This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with alanine at codon 6 of the SOD1 protein (p.Val6Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. This variant has not been reported in the literature in individuals affected with SOD1-related conditions. 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. 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
Publications
No publications associated with this variant yet.