ClinVar Genomic variation as it relates to human health
NM_025137.4(SPG11):c.1235C>G (p.Ser412Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_025137.4(SPG11):c.1235C>G (p.Ser412Ter)
Variation ID: 41269 Accession: VCV000041269.12
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 15q21.1 15: 44651712 (GRCh38) [ NCBI UCSC ] 15: 44943910 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline May 3, 2013 Feb 20, 2024 Jul 7, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_025137.4:c.1235C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_079413.3:p.Ser412Ter nonsense NM_001160227.2:c.1235C>G NP_001153699.1:p.Ser412Ter nonsense NC_000015.10:g.44651712G>C NC_000015.9:g.44943910G>C NG_008885.1:g.16967C>G - Protein change
- S412*
- Other names
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- Canonical SPDI
- NC_000015.10:44651711:G:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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SPG11 | - | - |
GRCh38 GRCh37 |
3218 | 3318 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Jul 7, 2023 | RCV000034170.15 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(May 31, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary spastic paraplegia 11
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000253952.7
First in ClinVar: Oct 11, 2015 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 41269). This premature translational stop signal … (more)
For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 41269). This premature translational stop signal has been observed in individual(s) with autosomal recessive hereditary spastic paraplegia (PMID: 18079167, 18663179, 27071356). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs312262723, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Ser412*) in the SPG11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SPG11 are known to be pathogenic (PMID: 19105190, 20110243, 22154821, 26556829). (less)
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Likely pathogenic
(Feb 03, 2017)
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criteria provided, single submitter
Method: clinical testing
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Hereditary spastic paraplegia 11
Affected status: yes
Allele origin:
unknown
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Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Accession: SCV000778411.1
First in ClinVar: Oct 11, 2015 Last updated: Oct 11, 2015 |
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Hereditary spastic paraplegia 11
Affected status: yes
Allele origin:
unknown
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Paris Brain Institute, Inserm - ICM
Accession: SCV001451243.1
First in ClinVar: May 16, 2021 Last updated: May 16, 2021 |
Number of individuals with the variant: 1
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Likely pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Hereditary spastic paraplegia 11
Affected status: unknown
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002764159.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
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Pathogenic
(Jul 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary spastic paraplegia 11
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV004045858.1
First in ClinVar: Oct 21, 2023 Last updated: Oct 21, 2023 |
Number of individuals with the variant: 1
Clinical Features:
Dystonic disorder (present) , Spastic paraplegia (present) , Spasticity (present) , Leukoencephalopathy (present)
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not provided
(-)
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no classification provided
Method: literature only
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Hereditary spastic paraplegia 11
Affected status: not provided
Allele origin:
unknown
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GeneReviews
Accession: SCV000058108.3
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Spastic Paraplegia 11. | Adam MP | - | 2019 | PMID: 20301389 |
High Frequency of Pathogenic Rearrangements in SPG11 and Extensive Contribution of Mutational Hotspots and Founder Alleles. | Günther S | Human mutation | 2016 | PMID: 27071356 |
ALS5/SPG11/KIAA1840 mutations cause autosomal recessive axonal Charcot-Marie-Tooth disease. | Montecchiani C | Brain : a journal of neurology | 2016 | PMID: 26556829 |
Exome sequencing reveals SPG11 mutations causing juvenile ALS. | Daoud H | Neurobiology of aging | 2012 | PMID: 22154821 |
SPATACSIN mutations cause autosomal recessive juvenile amyotrophic lateral sclerosis. | Orlacchio A | Brain : a journal of neurology | 2010 | PMID: 20110243 |
Screening of ARHSP-TCC patients expands the spectrum of SPG11 mutations and includes a large scale gene deletion. | Denora PS | Human mutation | 2009 | PMID: 19105190 |
SPG11 compound mutations in spastic paraparesis with thin corpus callosum. | Samaranch L | Neurology | 2008 | PMID: 18663179 |
Mutations in SPG11 are frequent in autosomal recessive spastic paraplegia with thin corpus callosum, cognitive decline and lower motor neuron degeneration. | Stevanin G | Brain : a journal of neurology | 2008 | PMID: 18079167 |
Text-mined citations for rs312262723 ...
HelpRecord last updated Apr 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.