rs911245988
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_025137.4(SPG11):c.32C>T(p.Ala11Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000294 in 1,596,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. A11P) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPG11 | NM_025137.4 | c.32C>T | p.Ala11Val | missense_variant | 1/40 | ENST00000261866.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPG11 | ENST00000261866.12 | c.32C>T | p.Ala11Val | missense_variant | 1/40 | 1 | NM_025137.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152266Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000140 AC: 3AN: 213614Hom.: 0 AF XY: 0.00000842 AC XY: 1AN XY: 118800
GnomAD4 exome AF: 0.0000298 AC: 43AN: 1443982Hom.: 0 Cov.: 32 AF XY: 0.0000293 AC XY: 21AN XY: 717914
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152266Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74396
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 11 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 03, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 11 of the SPG11 protein (p.Ala11Val). This variant is present in population databases (no rsID available, gnomAD 0.005%). 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: 570986). 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: "Not Available"; 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