VCV001174531.2 - ClinVar

NM_001039141.3(TRIOBP):c.3214dup (p.Arg1072fs)

Germline

Classification

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.

(2)

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.

Pathogenic

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001039141.3(TRIOBP):c.3214dup (p.Arg1072fs)

Variation ID: 1174531 Accession: VCV001174531.2

Type and length

Duplication, 1 bp

Location

Cytogenetic: 22q13.1 22: 37725764-37725765 (GRCh38) [ NCBI UCSC ] 22: 38121771-38121772 (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	Jan 1, 2022	Feb 20, 2024	Sep 22, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_001039141.3:c.3214dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001034230.1:p.Arg1072fs	frameshift
NC_000022.11:g.37725770dup
NC_000022.10:g.38121777dup
NG_012857.1:g.33783dup

Protein change

R1072fs

Other names

Canonical SPDI

NC_000022.11:37725764:CCCCCC:CCCCCCC

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

Links

dbSNP: rs1485334519 VarSome

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
Gene	OMIM	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	839	933

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.
Autosomal recessive nonsyndromic hearing loss 28	Pathogenic (1)	criteria provided, single submitter	Sep 3, 2020	RCV001799527.1
not provided	Pathogenic (1)	criteria provided, single submitter	Sep 22, 2023	RCV003660893.2

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 (Sep 03, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive nonsyndromic hearing loss 28 Affected status: yes Allele origin: germline	Center of Genomic medicine, Geneva, University Hospital of Geneva Accession: SCV001739309.1 First in ClinVar: Jan 01, 2022 Last updated: Jan 01, 2022	Number of individuals with the variant: 1 Age: 0-9 years Sex: female
Pathogenic (Sep 22, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004382655.1 First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024	Publications: PubMed (4) PubMed: 16385457‚ 16385458‚ 20510926‚ 34440452 Comment: This sequence change creates a premature translational stop signal (p.Arg1072Profs12) 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.Arg1072Profs12) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with deafness (PMID: 34440452). ClinVar contains an entry for this variant (Variation ID: 1174531). For these reasons, this variant has been classified as Pathogenic. (less)

Comment:

This sequence change creates a premature translational stop signal (p.Arg1072Profs*12) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with deafness (PMID: 34440452). ClinVar contains an entry for this variant (Variation ID: 1174531). For these reasons, this variant has been classified as Pathogenic.

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.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Benefits of Exome Sequencing in Children with Suspected Isolated Hearing Loss.	Van Heurck R	Genes	2021	PMID: 34440452
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

Text-mined citations for rs1485334519 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_001039141.3(TRIOBP):c.3214dup (p.Arg1072fs)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1485334519 ...