ClinVar Genomic variation as it relates to human health
NM_194248.3(OTOF):c.158C>T (p.Ala53Val)
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_194248.3(OTOF):c.158C>T (p.Ala53Val)
Variation ID: 21824 Accession: VCV000021824.31
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2p23.3 2: 26527901 (GRCh38) [ NCBI UCSC ] 2: 26750769 (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 4, 2013 Feb 20, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_194248.3:c.158C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_919224.1:p.Ala53Val missense NM_001287489.2:c.158C>T NP_001274418.1:p.Ala53Val missense NC_000002.12:g.26527901G>A NC_000002.11:g.26750769G>A NG_009937.1:g.35798C>T Q9HC10:p.Ala53Val - Protein change
- A53V
- Other names
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- Canonical SPDI
- NC_000002.12:26527900: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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0.10024 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.10024
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00361
The Genome Aggregation Database (gnomAD) 0.02762
Trans-Omics for Precision Medicine (TOPMed) 0.04603
Exome Aggregation Consortium (ExAC) 0.05373
The Genome Aggregation Database (gnomAD), exomes 0.06552
1000 Genomes Project 30x 0.09775
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
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
Help
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
Help
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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OTOF | - | - |
GRCh38 GRCh37 |
1948 | 2085 |
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
Help
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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Benign (3) |
criteria provided, multiple submitters, no conflicts
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May 4, 2022 | RCV000021036.16 | |
Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
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Dec 10, 2021 | RCV000041465.26 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV001811193.20 |
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
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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Benign
(-)
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criteria provided, single submitter
Method: clinical testing
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NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000316845.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Benign
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 9
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000429658.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
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 … (more)
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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
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Benign
(May 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 9
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002809674.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Benign
(Feb 01, 2024)
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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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Invitae
Accession: SCV002402533.3
First in ClinVar: Apr 12, 2022 Last updated: Feb 20, 2024 |
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Benign
(Nov 29, 2023)
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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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001156864.6
First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024 |
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Benign
(Sep 07, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000730601.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Benign
(Apr 29, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000340864.4
First in ClinVar: Dec 06, 2016 Last updated: Apr 09, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Benign
(Apr 23, 2010)
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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: SCV000065160.6
First in ClinVar: May 03, 2013 Last updated: Apr 09, 2018 |
Comment:
Ala53Val in exon 3 of OTOF: This variant is not expected to have clinical signif icance because it was detected in normal hearing controls and … (more)
Ala53Val in exon 3 of OTOF: This variant is not expected to have clinical signif icance because it was detected in normal hearing controls and it involves a chan ge at a position that is not conserved (Jiminez 2007, Varga 2006). In addition, it has been seen in an unpublished study with a minor allele frequency of 3% and has been identified in 10/122 (8%) of individuals tested by our laboratory. Thi s variant is also listed in dbSNP (rs1879761 - no frequency data available). (less)
Number of individuals with the variant: 197
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Likely benign
(Dec 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002051043.1
First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022 |
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not provided
(-)
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no classification provided
Method: literature only
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Autosomal recessive nonsyndromic hearing loss 9
Affected status: not provided
Allele origin:
unknown
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GeneReviews
Accession: SCV000041690.2
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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OTOF-Related Deafness. | Adam MP | - | 2021 | PMID: 20301429 |
OTOF mutation screening in Japanese severe to profound recessive hearing loss patients. | Iwasa Y | BMC medical genetics | 2013 | PMID: 24053799 |
In silico functional and structural characterisation of ferlin proteins by mapping disease-causing mutations and evolutionary information onto three-dimensional models of their C2 domains. | Jiménez JL | Journal of the neurological sciences | 2007 | PMID: 17512949 |
OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele. | Varga R | Journal of medical genetics | 2006 | PMID: 16371502 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=OTOF | - | - | - | - |
Text-mined citations for rs1879761 ...
HelpRecord last updated May 12, 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.