ClinVar Genomic variation as it relates to human health
NM_003119.4(SPG7):c.376+1G>T
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_003119.4(SPG7):c.376+1G>T
Variation ID: 411682 Accession: VCV000411682.37
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16q24.3 16: 89513038 (GRCh38) [ NCBI UCSC ] 16: 89579446 (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 Apr 17, 2017 May 12, 2024 Sep 8, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003119.4:c.376+1G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_001363850.1:c.376+1G>T splice donor NM_199367.3:c.376+1G>T splice donor NC_000016.10:g.89513038G>T NC_000016.9:g.89579446G>T NG_008082.1:g.9642G>T - Protein change
- Other names
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- Canonical SPDI
- NC_000016.10:89513037:G:T
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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
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00003
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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SPG7 | - | - |
GRCh38 GRCh37 |
915 | 1076 |
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
Help
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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Likely pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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Sep 8, 2023 | RCV000467232.11 | |
Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Oct 28, 2022 | RCV000522524.25 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Feb 14, 2023 | RCV003447529.2 |
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
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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
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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
Help
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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Likely pathogenic
(Aug 23, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000856581.1
First in ClinVar: Dec 19, 2017 Last updated: Dec 19, 2017 |
Number of individuals with the variant: 1
Sex: mixed
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Pathogenic
(Apr 23, 2019)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000617490.4
First in ClinVar: Dec 19, 2017 Last updated: Mar 04, 2023 |
Comment:
Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population … (more)
Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 23065789) (less)
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Likely pathogenic
(Sep 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary spastic paraplegia 7
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000552960.5
First in ClinVar: Apr 17, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change affects a donor splice site in intron 3 of the SPG7 gene. It is expected to disrupt RNA splicing. Variants that disrupt … (more)
This sequence change affects a donor splice site in intron 3 of the SPG7 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SPG7 are known to be pathogenic (PMID: 21623769, 22964162). This variant is present in population databases (rs746053679, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with hereditary spastic paraplegia (PMID: 23065789). ClinVar contains an entry for this variant (Variation ID: 411682). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
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Pathogenic
(Sep 01, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001246156.21
First in ClinVar: May 12, 2020 Last updated: May 12, 2024 |
Number of individuals with the variant: 1
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Likely pathogenic
(Aug 25, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary spastic paraplegia 7
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002572337.1
First in ClinVar: Sep 17, 2022 Last updated: Sep 17, 2022 |
Comment:
Variant summary: SPG7 c.376+1G>T is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to … (more)
Variant summary: SPG7 c.376+1G>T is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Four computational tools predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.2e-05 in 260534 control chromosomes (gnomAD). c.376+1G>T has been reported in the literature in at least one compound heterozygous individual affected with Spastic Paraplegia (Klebe_2012). These data do not allow any conclusion about variant significance. Five ClinVar submitters have assessed the variant since 2014: two classified the variant as likely pathogenic and three as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. (less)
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Likely pathogenic
(Dec 17, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary spastic paraplegia 7
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002801422.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Likely pathogenic
(Feb 14, 2023)
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criteria provided, single submitter
Method: clinical testing
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Early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV004175797.1
First in ClinVar: Dec 17, 2023 Last updated: Dec 17, 2023 |
Comment:
The invariant splice site c.376+1G>T variant in SPG7 gene has been reported in compound heterozygous state in an individuals affected with spastic paraplegia (Klebe S, … (more)
The invariant splice site c.376+1G>T variant in SPG7 gene has been reported in compound heterozygous state in an individuals affected with spastic paraplegia (Klebe S, et. al., 2012). The variant is reported with an allele frequency of 0.0009% in the gnomAD exomes database and is novel (not in any individuals) in 1000 Genomes database. This variant has been reported to the ClinVar database as Pathogenic/Likely pathogenic (multiple submissions). Loss of function variants have been previously reported to be disease causing. Functional studies are required to prove pathogenicity of the variant. For these reasons, this variant has been classified as Likely Pathogenic. In absence of another reportable variant in SPG7 gene, the molecular diagnosis is not confirmed. (less)
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Likely pathogenic
(Oct 28, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Athena Diagnostics
Accession: SCV004229207.1
First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024 |
Comment:
The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant is expected to impact normal RNA splicing, however, it … (more)
The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant is expected to impact normal RNA splicing, however, it is predicted to result in an in-frame change to the transcript. This variant has been identified in multiple unrelated individuals with clinical features associated with this gene. (less)
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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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Evidence for Non-Mendelian Inheritance in Spastic Paraplegia 7. | Estiar MA | Movement disorders : official journal of the Movement Disorder Society | 2021 | PMID: 33598982 |
Spastic paraplegia gene 7 in patients with spasticity and/or optic neuropathy. | Klebe S | Brain : a journal of neurology | 2012 | PMID: 23065789 |
Genotype-phenotype correlations in spastic paraplegia type 7: a study in a large Dutch cohort. | van Gassen KL | Brain : a journal of neurology | 2012 | PMID: 22964162 |
Amplicon-based high-throughput pooled sequencing identifies mutations in CYP7B1 and SPG7 in sporadic spastic paraplegia patients. | Schlipf NA | Clinical genetics | 2011 | PMID: 21623769 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SPG7 | - | - | - | - |
Text-mined citations for rs746053679 ...
HelpRecord last updated May 27, 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.