ClinVar Genomic variation as it relates to human health
m.961T>G
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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m.961T>G
Variation ID: 9633 Accession: VCV000009633.6
- Type and length
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single nucleotide variant, 1 bp
- Location
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MT: 961 (GRCh38) [ NCBI UCSC ] MT: 961 (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 Oct 11, 2015 May 19, 2019 Feb 6, 2015 - HGVS
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Nucleotide Protein Molecular
consequenceNC_012920.1:m.961T>G - Protein change
- Other names
- 961T-G
- Canonical SPDI
- NC_012920.1:960:T:G
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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
Help
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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MT-RNR1 | - | - | GRCh38 | 75 | 78 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
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
Help
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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Conflicting interpretations of pathogenicity (2) |
no assertion criteria provided
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Jun 14, 2018 | RCV000010264.6 | |
Likely benign (1) |
criteria provided, single submitter
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Feb 6, 2015 | RCV000035062.6 |
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
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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Likely benign
(Feb 06, 2015)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000058702.5
First in ClinVar: May 03, 2013 Last updated: May 29, 2016 |
Comment:
m.961T>G in MTRNR1: This variant is not expected to have clinical significance b ecause it has been reported in phylogenetic studies with a haplogroup-specific f … (more)
m.961T>G in MTRNR1: This variant is not expected to have clinical significance b ecause it has been reported in phylogenetic studies with a haplogroup-specific f requency in central Europeans of 98% (http://mitomap.org/MITOMAP, http://www.mtd b.igp.uu.se). Several studies have associated this variant with maternally inher ited hearing loss (Li 2004, Yelverton 2013). However, other studies have identif ied this variant as common in the general population with similar frequencies am ong hearing loss patients and controls (0.2% ? 3%) (Bardien 2009, Elstner 2008, Konings 2008, Rydzanicz 2010; 6 observations in the LOVD database http://www.lov d.nl/2.0; 0.2% (5/2704) in mtDB http://www.mtdb.igp.uu.se; 1% in HmtDB http://ww w.hmtdb.uniba.it:8080/hmdb). In addition, in one study there was no difference o bserved in the mitochondrial translation products with the m.961T>G mutation com pared to controls (Elstner 2008). Moreover, this region of mitochondrial DNA is not evolutionarily conserved and its function is not well defined. Of note, chic ken has guanine at position m.961 (Konings 2008). One study of cystic fibrosis a dult patients did not observe a correlation between this variant and aminoglycos ide ototoxicity (Conrad 2008). In summary, the current data for this variant sup ports a likely benign role. (less)
Number of individuals with the variant: 19
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Pathogenic
(Aug 01, 2004)
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no assertion criteria provided
Method: literature only
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DEAFNESS, NONSYNDROMIC SENSORINEURAL, MITOCHONDRIAL
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000030488.2
First in ClinVar: Apr 04, 2013 Last updated: Aug 27, 2017 |
Comment on evidence:
In 5 unrelated children with nonsyndromic sensorineural deafness (500008), Li et al. (2004) identified a homoplasmic 961T-G transversion in the MTRNR1 gene. These 5 patients … (more)
In 5 unrelated children with nonsyndromic sensorineural deafness (500008), Li et al. (2004) identified a homoplasmic 961T-G transversion in the MTRNR1 gene. These 5 patients exhibited distinct sets of mtDNA polymorphism in addition to the 961T-G mutation. The mutation was not found in 226 controls. Li et al. (2004) suggested that the MTRNR1 gene is a hotspot for deafness-associated mutations. (less)
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Uncertain significance
(Jun 14, 2018)
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no assertion criteria provided
Method: literature only
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Mitochondrial non-syndromic sensorineural hearing loss
Affected status: unknown
Allele origin:
maternal
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GeneReviews
Accession: SCV000172232.2
First in ClinVar: Oct 11, 2015 Last updated: May 19, 2019 |
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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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Nonsyndromic Hearing Loss and Deafness, Mitochondrial. | Adam MP | - | 2018 | PMID: 20301595 |
Association between idiopathic hearing loss and mitochondrial DNA mutations: a study on 169 hearing-impaired subjects. | Guaran V | International journal of molecular medicine | 2013 | PMID: 23969527 |
The clinical and audiologic features of hearing loss due to mitochondrial mutations. | Yelverton JC | Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery | 2013 | PMID: 23525847 |
Mutation analysis of mitochondrial 12S rRNA gene in Polish patients with non-syndromic and aminoglycoside-induced hearing loss. | Rydzanicz M | Biochemical and biophysical research communications | 2010 | PMID: 20353758 |
Infantile cardiomyopathy caused by a mutation in the overlapping region of mitochondrial ATPase 6 and 8 genes. | Ware SM | Journal of medical genetics | 2009 | PMID: 19188198 |
A rapid method for detection of five known mutations associated with aminoglycoside-induced deafness. | Bardien S | BMC medical genetics | 2009 | PMID: 19144107 |
Mitochondrial 12S rRNA susceptibility mutations in aminoglycoside-associated and idiopathic bilateral vestibulopathy. | Elstner M | Biochemical and biophysical research communications | 2008 | PMID: 18851951 |
Mutation analysis of mitochondrial DNA 12SrRNA and tRNASer(UCN) genes in non-syndromic hearing loss patients. | Konings A | Mitochondrion | 2008 | PMID: 18790089 |
The mitochondrial 13513G>A mutation is associated with Leigh disease phenotypes independent of complex I deficiency in muscle. | Brautbar A | Molecular genetics and metabolism | 2008 | PMID: 18495510 |
Molecular bases of hearing loss in multi-systemic mitochondrial cytopathy. | Scaglia F | Genetics in medicine : official journal of the American College of Medical Genetics | 2006 | PMID: 17079881 |
Secondary metabolic effects in complex I deficiency. | Esteitie N | Annals of neurology | 2005 | PMID: 16044424 |
Molecular analysis of the mitochondrial 12S rRNA and tRNASer(UCN) genes in paediatric subjects with non-syndromic hearing loss. | Li R | Journal of medical genetics | 2004 | PMID: 15286157 |
Genetic susceptibility to aminoglycoside ototoxicity: how many are at risk? | Tang HY | Genetics in medicine : official journal of the American College of Medical Genetics | 2002 | PMID: 12394346 |
Sequence analysis of the entire mitochondrial genome in Parkinson's disease. | Vives-Bauza C | Biochemical and biophysical research communications | 2002 | PMID: 11820805 |
Gueran 23969527 | - | - | - | - |
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Text-mined citations for rs3888511 ...
HelpRecord last updated Feb 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.