rs760815236
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_025137.4(SPG11):āc.5645T>Gā(p.Ile1882Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,888 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I1882T) 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 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPG11 | NM_025137.4 | c.5645T>G | p.Ile1882Ser | missense_variant | 30/40 | ENST00000261866.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPG11 | ENST00000261866.12 | c.5645T>G | p.Ile1882Ser | missense_variant | 30/40 | 1 | NM_025137.4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251444Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135896
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461888Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727246
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 11 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 12, 2022 | This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1882 of the SPG11 protein (p.Ile1882Ser). This variant is present in population databases (rs760815236, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with SPG11-related conditions. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at