15-44573661-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_025137.4(SPG11):c.6091C>G(p.Arg2031Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R2031Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_025137.4 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 |
---|---|---|---|---|---|---|---|
SPG11 | NM_025137.4 | c.6091C>G | p.Arg2031Gly | missense_variant | 32/40 | ENST00000261866.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPG11 | ENST00000261866.12 | c.6091C>G | p.Arg2031Gly | missense_variant | 32/40 | 1 | NM_025137.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152154Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251360Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135854
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461886Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 727244
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74322
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 11 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2022 | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 2031 of the SPG11 protein (p.Arg2031Gly). This variant is present in population databases (rs147713329, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with SPG11-related conditions. ClinVar contains an entry for this variant (Variation ID: 220392). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 03, 2022 | The p.R2031G variant (also known as c.6091C>G), located in coding exon 32 of the SPG11 gene, results from a C to G substitution at nucleotide position 6091. The arginine at codon 2031 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2019 | - - |
Amyotrophic lateral sclerosis type 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
Charcot-Marie-Tooth disease axonal type 2X Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at