ClinVar Genomic variation as it relates to human health
NM_001393500.2(TOMT):c.143G>A (p.Arg48Gln)
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_001393500.2(TOMT):c.143G>A (p.Arg48Gln)
Variation ID: 543 Accession: VCV000000543.6
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q13.4 11: 72106094 (GRCh38) [ NCBI UCSC ] 11: 71817140 (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 Oct 15, 2022 Jul 29, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001393500.2:c.143G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001380429.1:p.Arg48Gln missense NM_001145308.5:c.242G>A NP_001138780.1:p.Arg81Gln missense NM_001145309.4:c.242G>A NP_001138781.1:p.Arg81Gln missense NM_001145310.4:c.122G>A NP_001138782.1:p.Arg41Gln missense NC_000011.10:g.72106094G>A NC_000011.9:g.71817140G>A NG_021423.1:g.30759G>A Q8WZ04:p.Arg81Gln - Protein change
- R81Q, R41Q, R48Q
- Other names
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- Canonical SPDI
- NC_000011.10:72106093: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.
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00003
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
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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LRTOMT | - | - |
GRCh38 GRCh37 |
23 | 236 | |
TOMT | - | - | - | GRCh38 | - | 121 |
Conditions - Germline
Condition
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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
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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 (3) |
criteria provided, multiple submitters, no conflicts
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Jul 29, 2022 | RCV000000573.4 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 9, 2018 | RCV000603810.4 |
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
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
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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
(Aug 09, 2018)
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criteria provided, single submitter
Method: clinical testing
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Rare genetic deafness
(Autosomal recessive inheritance)
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000731644.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
Comment:
The p.Arg81Gln variant in LRTOMT has been reported in 16 North African (Tunisian and Moroccan) probands with hearing loss, and segregated with hearing loss in … (more)
The p.Arg81Gln variant in LRTOMT has been reported in 16 North African (Tunisian and Moroccan) probands with hearing loss, and segregated with hearing loss in > 20 family members, all of whom were homozygous for the variant (Ahmed 2008, Char if 2008). The variant was detected in 5/430 (1.2%) ethnically matched control ch romosomes, however its frequency in the probands (13.8%, 32/232 chromosomes) is significantly higher, which supports a causative role for the variant, and sugge sts that the variant may represent a founder mutation in these populations. In a ddition, computational prediction tools and conservation analyses suggest that t his variant may impact the protein. The variant has also been identified in 3/57 674 European chromosomes by the genome Aggregation Database (gnomAD, http://gnom ad.broadinstitute.org/). In summary, this variant meets criteria to be classifie d as pathogenic for hearing loss in an autosomal recessive manner based upon seg regation studies and enrichment in cases. ACMG/AMP criteria applied: PS4, PP1_St rong, PP3. (less)
Number of individuals with the variant: 2
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Pathogenic
(Jan 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 63
Affected status: yes
Allele origin:
germline
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3billion
Accession: SCV002059017.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
Comment:
The variant was co-segregated with Deafness, autosomal recessive 63 in multiple affected family members with additional meioses meeting strong evidence levels (PMID: 18953341, PP1_S). It … (more)
The variant was co-segregated with Deafness, autosomal recessive 63 in multiple affected family members with additional meioses meeting strong evidence levels (PMID: 18953341, PP1_S). It has been reported to be in trans as homozygous in at least one similarly affected unrelated individual (PMID: 18953341,PM3_P). A different missense change at the same codon has been reported to be associated with LRTOMT related disorder (PMID:22903915, PM5_P). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.701, PP3_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000026, PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Hearing impairment (present)
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Pathogenic
(Jul 29, 2022)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 63
Affected status: yes
Allele origin:
germline
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MGZ Medical Genetics Center
Accession: SCV002581628.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022 |
Number of individuals with the variant: 1
Sex: male
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Pathogenic
(Nov 01, 2008)
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no assertion criteria provided
Method: literature only
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DEAFNESS, AUTOSOMAL RECESSIVE 63
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000020722.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
In affected individuals of a Tunisian family with DFNB63 (611451), Ahmed et al. (2008) identified a homozygous 242G-A transition in exon 8 of the LRTOMT … (more)
In affected individuals of a Tunisian family with DFNB63 (611451), Ahmed et al. (2008) identified a homozygous 242G-A transition in exon 8 of the LRTOMT gene, resulting in an arg81-to-gln (R81Q) substitution predicted to alter the COMT domain of LRTOMT2. (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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The c.242G>A mutation in LRTOMT gene is responsible for a high prevalence of deafness in the Moroccan population. | Charif M | Molecular biology reports | 2012 | PMID: 23053991 |
Founder mutations in Tunisia: implications for diagnosis in North Africa and Middle East. | Romdhane L | Orphanet journal of rare diseases | 2012 | PMID: 22908982 |
A comprehensive study to determine heterogeneity of autosomal recessive nonsyndromic hearing loss in Iran. | Babanejad M | American journal of medical genetics. Part A | 2012 | PMID: 22903915 |
Mutations of LRTOMT, a fusion gene with alternative reading frames, cause nonsyndromic deafness in humans. | Ahmed ZM | Nature genetics | 2008 | PMID: 18953341 |
Text-mined citations for rs137853185 ...
HelpRecord last updated Dec 25, 2023
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.