ClinVar Genomic variation as it relates to human health
NM_005422.4(TECTA):c.5383+5_5383+8del
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_005422.4(TECTA):c.5383+5_5383+8del
Variation ID: 1185582 Accession: VCV001185582.6
- Type and length
-
Microsatellite, 4 bp
- Location
-
Cytogenetic: 11q23.3 11: 121165383-121165386 (GRCh38) [ NCBI UCSC ] 11: 121036092-121036095 (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 21, 2021 Feb 14, 2024 Jul 13, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_005422.4:c.5383+5_5383+8del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_001378761.1:c.6325+5_6325+8del splice donor NC_000011.10:g.121165384GTGA[1] NC_000011.9:g.121036093GTGA[1] NG_011633.1:g.67719GTGA[1] - Protein change
- Other names
- -
- Canonical SPDI
- NC_000011.10:121165382:AGTGAGTGA:AGTGA
-
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.
-
- Links
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. |
|||
TBCEL-TECTA | - | - | - | GRCh38 | - | 1026 |
TECTA | - | - |
GRCh38 GRCh37 |
- | 1042 |
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 (1) |
criteria provided, single submitter
|
- | RCV001730849.1 | |
Pathogenic (1) |
criteria provided, single submitter
|
May 22, 2022 | RCV002250765.1 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Jul 13, 2023 | RCV002568953.3 |
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
(-)
|
criteria provided, single submitter
Method: research, in vitro
|
Bilateral sensorineural hearing impairment
Affected status: not applicable, yes
Allele origin:
germline,
not applicable
|
Laboratory of Human Genetics, Institute of Biosciences - University of Sao Paulo
Accession: SCV001762976.1
First in ClinVar: Oct 21, 2021 Last updated: Oct 21, 2021 |
Comment:
The c.5383+5_5383+8del variant was dound to segregate with nonsynddromic postlingual stable hearing loss in nine affected subjects from a Brazilian family. Analysis of the mRNA … (more)
The c.5383+5_5383+8del variant was dound to segregate with nonsynddromic postlingual stable hearing loss in nine affected subjects from a Brazilian family. Analysis of the mRNA of lympholastoid cells from one carrier affected individual revealed na aberrant transcript with skipped eoxn 16 (less)
Observation 1:
Clinical Features:
Prelingual sensorineural hearing impairment (present)
Family history: yes
Segregation observed: yes
Secondary finding: no
Observation 2:
Clinical Features:
Prelingual sensorineural hearing impairment (present)
Family history: yes
Segregation observed: yes
Secondary finding: no
Observation 3:
Clinical Features:
Prelingual sensorineural hearing impairment (present)
Family history: yes
Segregation observed: yes
Secondary finding: no
Observation 4:
Clinical Features:
Prelingual sensorineural hearing impairment (present)
Family history: yes
Segregation observed: yes
Secondary finding: no
Observation 5:
Clinical Features:
Prelingual sensorineural hearing impairment (present)
Family history: yes
Segregation observed: yes
Secondary finding: no
Observation 6:
Clinical Features:
Prelingual sensorineural hearing impairment (present)
Family history: yes
Segregation observed: yes
Secondary finding: no
Observation 7:
Clinical Features:
Prelingual sensorineural hearing impairment (present)
Family history: yes
Segregation observed: yes
Secondary finding: no
Observation 8:
Clinical Features:
Prelingual sensorineural hearing impairment (present)
Family history: yes
Segregation observed: yes
Secondary finding: no
Observation 9:
Clinical Features:
Prelingual sensorineural hearing impairment (present)
Family history: yes
Segregation observed: yes
Secondary finding: no
Observation 10:
Tissue: Blood
Method: RT-PCR; Sanger Seq
Result:
aberrant transcript with skipping of exon 16
|
|
Pathogenic
(May 22, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal dominant nonsyndromic hearing loss 12
Affected status: yes
Allele origin:
germline
|
3billion
Accession: SCV002521332.1
First in ClinVar: Jun 03, 2022 Last updated: Jun 03, 2022 |
Comment:
The variant is not observed in the gnomAD v2.1.1 dataset. Canonical splice site: previously reported to alter splicing. The variant has been observed experimentally to … (more)
The variant is not observed in the gnomAD v2.1.1 dataset. Canonical splice site: previously reported to alter splicing. The variant has been observed experimentally to skip exon 16 of NM_005422.4 transcript resulting in frame deletion. (PMID : 22995349). The variant has been reported to co-segregate with the disease in at least 5 similarly affected relatives/individuals in the same family or similarly affected unrelated families (PMID: 22995349). The variant has been reported to be associated with TECTA related disorder (ClinVar ID: VCV001185582 / PMID: 21520338). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Hearing impairment (present)
|
|
Pathogenic
(Nov 21, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV003923803.1
First in ClinVar: May 13, 2023 Last updated: May 13, 2023 |
Comment:
Intronic +5 splice site variant with both splice predictors and evolutionary conservation supporting a deleterious effect; published in vitro studies demonstrate an aberrant transcript with … (more)
Intronic +5 splice site variant with both splice predictors and evolutionary conservation supporting a deleterious effect; published in vitro studies demonstrate an aberrant transcript with in-frame skipping of exon 16 (Lezirovitz et al., 2012); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 31725169, 33297549, 28419064, 21520338, 22995349) (less)
|
|
Pathogenic
(Jul 13, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV003441186.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
This sequence change falls in intron 16 of the TECTA gene. It does not directly change the encoded amino acid sequence of the TECTA protein. … (more)
This sequence change falls in intron 16 of the TECTA gene. It does not directly change the encoded amino acid sequence of the TECTA protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with autosomal dominant deafness (PMID: 22995349). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1185582). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 16, but is expected to preserve the integrity of the reading-frame (PMID: 22995349). For these reasons, this variant has been classified as Pathogenic. (less)
|
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 |
---|---|---|---|---|
Genetic etiology of non-syndromic hearing loss in Latin America. | Lezirovitz K | Human genetics | 2022 | PMID: 34652575 |
Aberrant transcript produced by a splice donor site deletion in the TECTA gene is associated with autosomal dominant deafness in a Brazilian family. | Lezirovitz K | Gene | 2012 | PMID: 22995349 |
DFNA8/12 caused by TECTA mutations is the most identified subtype of nonsyndromic autosomal dominant hearing loss. | Hildebrand MS | Human mutation | 2011 | PMID: 21520338 |
Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. | Buratti E | Nucleic acids research | 2007 | PMID: 17576681 |
Statistical features of human exons and their flanking regions. | Zhang MQ | Human molecular genetics | 1998 | PMID: 9536098 |
Text-mined citations for rs2135128814 ...
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.