ClinVar Genomic variation as it relates to human health
NM_001039141.3(TRIOBP):c.1039C>T (p.Arg347Ter)
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
-
NM_001039141.3(TRIOBP):c.1039C>T (p.Arg347Ter)
Variation ID: 1490 Accession: VCV000001490.11
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 22q13.1 22: 37723595 (GRCh38) [ NCBI UCSC ] 22: 38119602 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 23, 2016 Feb 14, 2024 Jul 7, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_001039141.3:c.1039C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001034230.1:p.Arg347Ter nonsense NC_000022.11:g.37723595C>T NC_000022.10:g.38119602C>T NG_012857.1:g.31608C>T - Protein change
- R347*
- Other names
- -
- Canonical SPDI
- NC_000022.11:37723594:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00005
The Genome Aggregation Database (gnomAD) 0.00010
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 | ||
---|---|---|---|---|---|---|
HI score
Help
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. |
|||
TRIOBP | - | - |
GRCh38 GRCh37 |
802 | 896 |
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. |
---|---|---|---|---|
Pathogenic (3) |
criteria provided, single submitter
|
Mar 22, 2022 | RCV000001555.6 | |
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Jul 7, 2023 | RCV000727382.10 |
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. |
|
---|---|---|---|---|---|
Pathogenic
(May 05, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000708022.2
First in ClinVar: Apr 03, 2017 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
|
Pathogenic
(Mar 22, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive nonsyndromic hearing loss 28
Affected status: yes
Allele origin:
germline
|
3billion
Accession: SCV002318557.1
First in ClinVar: Apr 02, 2022 Last updated: Apr 02, 2022 |
Comment:
Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are … (more)
Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. This variant has been reported as pathogenic (ClinVar ID: VCV000001490, PMID:16385458). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.0000399). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Hearing impairment (present)
|
|
Pathogenic
(Jul 15, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV002820484.1
First in ClinVar: Jan 21, 2023 Last updated: Jan 21, 2023 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 25525159, 30833958, 32747562, 33121024, 16385458, 32279305) (less)
|
|
Pathogenic
(Jul 07, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV002244599.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg347*) in the TRIOBP gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg347*) in the TRIOBP gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TRIOBP are known to be pathogenic (PMID: 16385457, 16385458, 20510926). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1490). This premature translational stop signal has been observed in individual(s) with nonsyndromic deafness (PMID: 16385458). This variant is present in population databases (rs118204026, gnomAD 0.01%). (less)
|
|
Pathogenic
(Jan 01, 2006)
|
no assertion criteria provided
Method: literature only
|
DEAFNESS, AUTOSOMAL RECESSIVE 28
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000021710.2
First in ClinVar: Apr 04, 2013 Last updated: Oct 23, 2016 |
Comment on evidence:
In members of a Palestinian Orthodox Christian family with autosomal recessive deafness (DFNB28; 609823), Shahin et al. (2006) found homozygosity for a 1039C-T transition in … (more)
In members of a Palestinian Orthodox Christian family with autosomal recessive deafness (DFNB28; 609823), Shahin et al. (2006) found homozygosity for a 1039C-T transition in coding exon 5 of the long TRIOBP isoform. The mutation was predicted to cause an arg347-to-stop (R347X) nonsense mutation. The hearing loss was sensorineural, bilateral, symmetric, and profound. The family traced its ancestry since the mid-18th century to the area of Bethlehem and Beit Sahour in Israel. The R347X mutations was also found in 3 other families from the same Orthodox Christian community. (less)
|
|
Pathogenic
(Jun 04, 2016)
|
no assertion criteria provided
Method: research
|
Autosomal recessive nonsyndromic hearing loss 28
Affected status: yes
Allele origin:
germline
|
Hereditary Research Laboratory, Bethlehem University
Accession: SCV000538125.1
First in ClinVar: Apr 03, 2017 Last updated: Apr 03, 2017 |
Comment:
Severe to Profound
|
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 |
---|---|---|---|---|
Actin-bundling protein TRIOBP forms resilient rootlets of hair cell stereocilia essential for hearing. | Kitajiri S | Cell | 2010 | PMID: 20510926 |
Mutations in a novel isoform of TRIOBP that encodes a filamentous-actin binding protein are responsible for DFNB28 recessive nonsyndromic hearing loss. | Shahin H | American journal of human genetics | 2006 | PMID: 16385458 |
Mutations in TRIOBP, which encodes a putative cytoskeletal-organizing protein, are associated with nonsyndromic recessive deafness. | Riazuddin S | American journal of human genetics | 2006 | PMID: 16385457 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=TRIOBP | - | - | - | - |
Text-mined citations for rs118204026 ...
HelpRecord last updated Feb 20, 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.