ClinVar Genomic variation as it relates to human health
NM_005422.4(TECTA):c.2657A>G (p.Asn886Ser)
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.
Uncertain significance(7); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_005422.4(TECTA):c.2657A>G (p.Asn886Ser)
Variation ID: 229296 Accession: VCV000229296.22
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q23.3 11: 121129927 (GRCh38) [ NCBI UCSC ] 11: 121000636 (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 May 29, 2016 Apr 15, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_005422.4:c.2657A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_005413.2:p.Asn886Ser missense NM_001378761.1:c.3614A>G NP_001365690.1:p.Asn1205Ser missense NC_000011.10:g.121129927A>G NC_000011.9:g.121000636A>G NG_011633.1:g.32262A>G O75443:p.Asn886Ser - Protein change
- N886S, N1205S
- Other names
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- Canonical SPDI
- NC_000011.10:121129926:A:G
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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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0.00060 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00040
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00046
1000 Genomes Project 30x 0.00047
The Genome Aggregation Database (gnomAD), exomes 0.00048
Trans-Omics for Precision Medicine (TOPMed) 0.00053
1000 Genomes Project 0.00060
The Genome Aggregation Database (gnomAD) 0.00061
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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LOC126861365 | - | - | - | GRCh38 | - | 111 |
TBCEL-TECTA | - | - | - | GRCh38 | - | 1059 |
TECTA | - | - |
GRCh38 GRCh37 |
- | 1066 |
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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Uncertain significance (1) |
criteria provided, single submitter
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Nov 27, 2019 | RCV000219728.6 | |
Uncertain significance (1) |
criteria provided, single submitter
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Apr 28, 2017 | RCV001103540.4 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Aug 28, 2019 | RCV001108703.5 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Feb 1, 2024 | RCV001582738.13 | |
Uncertain significance (1) |
criteria provided, single submitter
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Sep 8, 2021 | RCV002500716.1 |
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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Uncertain significance
(Apr 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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Autosomal dominant nonsyndromic hearing loss 12
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001260312.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Uncertain significance
(Apr 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 21
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001265972.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Uncertain significance
(Nov 27, 2019)
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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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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000272484.4
First in ClinVar: May 29, 2016 Last updated: Jul 03, 2020 |
Comment:
The p.Asn886Ser variant in TECTA has been previously reported in 7 individuals with sensorineural hearing loss (Baux 2017, Hildebrand 2011, Sommen 2016, Baux 2017, LMM … (more)
The p.Asn886Ser variant in TECTA has been previously reported in 7 individuals with sensorineural hearing loss (Baux 2017, Hildebrand 2011, Sommen 2016, Baux 2017, LMM data). In 3 of these individuals a second TECTA variant was identified (p.Glu1950del, p.Val205Leu, p.Cys1372*), though only one was likely to be pathogenic (p.Cys1372*). Furthermore, one of the previously reported probands had a family history of autosomal dominant hearing loss, and while the variant segregated with the disease in 12 affected family members, a more likely pathogenic variant in TECTA (c.5383+5_5383+8delGTGA) was identified in cis with p.Asn886Ser, suggesting that p.Asn886Ser was less likely related to the hearing loss in this family (Hildebrand, 2011). This variant has been identified in 0.07% (98/128646) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that the p.Asn886Ser variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, due to conflicting evidence, the clinical significance of the p.Asn886Ser variant is uncertain. ACMG/AMP Criteria applied: PM3, PP3, BS1_Supporting, BP2. (less)
Number of individuals with the variant: 5
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Uncertain significance
(Aug 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 21
Affected status: yes
Allele origin:
germline
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Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002769534.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
A heterozygous missense variant, NM_005422.2(TECTA):c.2657A>G, has been identified in exon 9 of 23 of the TECTA gene. The variant is predicted to result in a … (more)
A heterozygous missense variant, NM_005422.2(TECTA):c.2657A>G, has been identified in exon 9 of 23 of the TECTA gene. The variant is predicted to result in a minor amino acid change from asparagine to serine at position 886 of the protein (NP_005413.2(TECTA):p.Asn886Ser). The asparagine residue at this position has high conservation (100 vertebrates, UCSC), and is located within the VWFD 2 functional domain. In silico predictions for this variant are conflicting (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD database at a frequency of 0.046% (130 heterozygotes). The variant has been previously described as a VUS and likely benign (ClinVar, Deafnessvariationdatabase, LOVD, Shearer, A. E., et al. (2014), Baux, D., et al. (2017)). An alternative change to histidine has also been reported as a VUS (Deafnessvariationdatabase). Based on the information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE with LOW CLINICAL RELEVANCE. (less)
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Uncertain significance
(Sep 08, 2021)
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criteria provided, single submitter
Method: clinical testing
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Autosomal dominant nonsyndromic hearing loss 12
Autosomal recessive nonsyndromic hearing loss 21
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002805560.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Uncertain significance
(May 26, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001812627.5
First in ClinVar: Sep 08, 2021 Last updated: Jun 03, 2023 |
Comment:
Reported in published literature in association with autosomal dominant non-syndromic hearing loss in one family, where it was identified in cis with a splicing variant … (more)
Reported in published literature in association with autosomal dominant non-syndromic hearing loss in one family, where it was identified in cis with a splicing variant in the TECTA gene in all affected individuals tested (Hildebrand et al., 2011); Located in the von Willebrand factor type D2 subdomain of the zonadhesin domain (Hildebrand et al., 2011); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25262649, 22995349, 27368438, 30245029, 21520338, 27068579, 29196752, 31554319, 9590290) (less)
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Likely benign
(Jan 13, 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: SCV002304431.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
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Uncertain significance
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004700479.2
First in ClinVar: Mar 10, 2024 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 1
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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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Combined genetic approaches yield a 48% diagnostic rate in a large cohort of French hearing-impaired patients. | Baux D | Scientific reports | 2017 | PMID: 29196752 |
DNA Diagnostics of Hereditary Hearing Loss: A Targeted Resequencing Approach Combined with a Mutation Classification System. | Sommen M | Human mutation | 2016 | PMID: 27068579 |
Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants. | Shearer AE | American journal of human genetics | 2014 | PMID: 25262649 |
DFNA8/12 caused by TECTA mutations is the most identified subtype of nonsyndromic autosomal dominant hearing loss. | Hildebrand MS | Human mutation | 2011 | PMID: 21520338 |
Text-mined citations for rs146175803 ...
HelpRecord last updated Apr 15, 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.