ClinVar Genomic variation as it relates to human health
NM_003143.3(SSBP1):c.320G>A (p.Arg107Gln)
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_003143.3(SSBP1):c.320G>A (p.Arg107Gln)
Variation ID: 977503 Accession: VCV000977503.19
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q34 7: 141445301 (GRCh37) [ NCBI UCSC ] 7: 141745501 (GRCh38) [ 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 Sep 9, 2020 Aug 4, 2024 Jan 17, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_003143.3:c.320G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003134.1:p.Arg107Gln missense NM_001256510.1:c.320G>A NP_001243439.1:p.Arg107Gln missense NM_001256511.1:c.320G>A NP_001243440.1:p.Arg107Gln missense NM_001256512.1:c.320G>A NP_001243441.1:p.Arg107Gln missense NM_001256513.1:c.320G>A NP_001243442.1:p.Arg107Gln missense NR_046269.1:n.503G>A non-coding transcript variant NC_000007.14:g.141745501G>A NC_000007.13:g.141445301G>A - Protein change
- R107Q
- Other names
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- Canonical SPDI
- NC_000007.14:141745500:G:A
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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.
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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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SSBP1 | - | - |
GRCh38 GRCh38 GRCh37 |
13 | 60 |
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 (2) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2021 | RCV001268036.16 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Jan 17, 2024 | RCV001255185.4 |
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
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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
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001446629.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Optic atrophy (present) , Rod-cone dystrophy (present)
Sex: male
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Pathogenic
(May 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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Optic atrophy 13 with retinal and foveal abnormalities
Affected status: yes
Allele origin:
germline
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3billion
Accession: SCV002521243.1
First in ClinVar: May 28, 2022 Last updated: May 28, 2022 |
Comment:
The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. Functional studies provide strong evidence of the variant … (more)
The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID:31298765). In silico tool predictions suggest no damaging effect of the variant on gene or gene product (REVEL: 0.24; 3Cnet: 0.14). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with SSBP1 related disorder (ClinVar ID: VCV000977503 / PMID: 31298765 / 3billion dataset). The variant has been previously reported as assumed (i.e. paternity and maternity not confirmed) de novo in at least one similarly affected unrelated individual (PMID:31298765). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Retinal degeneration (present) , Optic atrophy (present)
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Pathogenic
(May 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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Optic atrophy 13 with retinal and foveal abnormalities
Affected status: unknown
Allele origin:
germline
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Mendelics
Accession: SCV002519819.1
First in ClinVar: May 28, 2022 Last updated: May 28, 2022 |
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Pathogenic
(Jan 17, 2024)
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criteria provided, single submitter
Method: clinical testing
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Optic atrophy 13 with retinal and foveal abnormalities
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV004244366.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
Criteria applied: PS4,PS3_MOD,PS2_MOD,PM2_SUP,PP1
Clinical Features:
Nephronophthisis (present) , Kidney disorder (present) , Hypertensive disorder (present) , Hyperechogenic kidneys (present) , Proteinuria (present) , Renal insufficiency (present) , Optic atrophy (present)
Sex: male
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Pathogenic
(Feb 01, 2021)
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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: SCV002563981.14
First in ClinVar: Aug 23, 2022 Last updated: Aug 04, 2024 |
Number of individuals with the variant: 1
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Pathogenic
(Sep 03, 2020)
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no assertion criteria provided
Method: literature only
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OPTIC ATROPHY 13 WITH RETINAL AND FOVEAL ABNORMALITIES
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV001431539.1
First in ClinVar: Sep 09, 2020 Last updated: Sep 09, 2020 |
Comment on evidence:
In multiple affected members of a large multigenerational kindred (family 1) with optic atrophy-13 with retinal and foveal abnormalities (OPA13; 165510), Jurkute et al. (2019) … (more)
In multiple affected members of a large multigenerational kindred (family 1) with optic atrophy-13 with retinal and foveal abnormalities (OPA13; 165510), Jurkute et al. (2019) identified a heterozygous c.320G-A transition (c.320G-A, NM_001256510.1) in exon 6 of the SSBP1 gene, resulting in an arg107-to-gln (R107Q) substitution at a conserved residue in the SSB domain. The mutation, which was found by a combination of linkage analysis and candidate gene sequencing, segregated with the disorder in the family. Functional studies in zebrafish showed that the R107Q mutation caused a reduction in retinal atoh7 (609875) expression and acted in a dominant-negative manner. There was no evidence of mtDNA deletions in blood samples in this family. In an Italian father and son (family 1) with OPA13, Del Dotto et al. (2020) identified a heterozygous R107Q mutation in the SSBP1 gene. The mutation, which was found by exome sequencing, arose de novo in the father. Western blot analysis of patient fibroblasts showed that levels of the R107Q mutant were similar to controls. However, in vitro protein crosslinking experiments showed that the R107Q variant interfered with SSBP1 multimerization. Patient fibroblasts showed significant mtDNA depletion, decreased ability to stimulate POLG1-induced mtDNA synthesis, and a decreased mitochondrial oxidative respiratory rate compared to controls, all of which were consistent with mitochondrial dysfunction. Expression of the R107Q mutation into ssbp1-null zebrafish failed to rescue the abnormal optic nerve phenotype, suggesting that the mutation causes a loss of function. In 3 probands (families C, D, and E) with OPA13, Piro-Megy et al. (2020) identified a heterozygous R107Q mutation of the SSBP1 gene. The mutations was found by direct screening of the gene. Segregation studies in the families and functional studies of the variant were not performed. (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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SSBP1 mutations cause mtDNA depletion underlying a complex optic atrophy disorder. | Del Dotto V | The Journal of clinical investigation | 2020 | PMID: 31550240 |
Dominant mutations in mtDNA maintenance gene SSBP1 cause optic atrophy and foveopathy. | Piro-Mégy C | The Journal of clinical investigation | 2020 | PMID: 31550237 |
SSBP1 mutations in dominant optic atrophy with variable retinal degeneration. | Jurkute N | Annals of neurology | 2019 | PMID: 31298765 |
Text-mined citations for rs1799747454 ...
HelpRecord last updated Aug 04, 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.