rs201082396
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_025137.4(SPG11):āc.3425C>Gā(p.Ser1142Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000905 in 1,614,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_025137.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPG11 | NM_025137.4 | c.3425C>G | p.Ser1142Cys | missense_variant | 19/40 | ENST00000261866.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPG11 | ENST00000261866.12 | c.3425C>G | p.Ser1142Cys | missense_variant | 19/40 | 1 | NM_025137.4 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000955 AC: 24AN: 251414Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135874
GnomAD4 exome AF: 0.0000930 AC: 136AN: 1461850Hom.: 0 Cov.: 31 AF XY: 0.0000976 AC XY: 71AN XY: 727228
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152292Hom.: 0 Cov.: 32 AF XY: 0.0000940 AC XY: 7AN XY: 74460
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 11 Uncertain:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | - | - - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Apr 01, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 02, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
SPG11-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 13, 2023 | The SPG11 c.3425C>G variant is predicted to result in the amino acid substitution p.Ser1142Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.023% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/15-44900670-G-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Hereditary spastic paraplegia 11;C1865864:Amyotrophic lateral sclerosis type 5;C5569024:Charcot-Marie-Tooth disease axonal type 2X Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 18, 2022 | - - |
Amyotrophic lateral sclerosis Uncertain:1
Uncertain significance, criteria provided, single submitter | case-control | UM ALS/MND Lab, University Of Malta | Sep 09, 2020 | - - |
Hereditary spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Mar 30, 2021 | - - |
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