rs150746549
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_025137.4(SPG11):c.2087T>G(p.Ile696Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,613,816 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. I696F) 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.2087T>G | p.Ile696Ser | missense_variant | 11/40 | ENST00000261866.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPG11 | ENST00000261866.12 | c.2087T>G | p.Ile696Ser | missense_variant | 11/40 | 1 | NM_025137.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152220Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250862Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135582
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461596Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727086
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74366
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 19, 2023 | The c.2087T>G (p.I696S) alteration is located in exon 11 (coding exon 11) of the SPG11 gene. This alteration results from a T to G substitution at nucleotide position 2087, causing the isoleucine (I) at amino acid position 696 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Hereditary spastic paraplegia 11 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2022 | This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 696 of the SPG11 protein (p.Ile696Ser). This variant is present in population databases (rs150746549, gnomAD 0.02%). 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: 466512). 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: "Benign"; 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