VCV000178539.26 - ClinVar

NM_005422.4(TECTA):c.3492C>T (p.Thr1164=)

Germline

Top reviewed classifications are shown here.

Submission summary:

8 submissions

7 submitters

6 conditions

Reviewed by expert panel

Likely benign

Feb 2019 by ClinGen Hearin… FDA Recognized Database

for Nonsyndromic genetic hearing loss

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_005422.4(TECTA):c.3492C>T (p.Thr1164=)

Variation ID: 178539 Accession: VCV000178539.26

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11q23.3 11: 121137971 (GRCh38) [ NCBI UCSC ] 11: 121008680 (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	Dec 6, 2016	Oct 8, 2024	Feb 13, 2019

HGVS

Nucleotide	Protein	Molecular consequence
NM_005422.4:c.3492C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_005413.2:p.Thr1164=	synonymous
NM_001378761.1:c.4449C>T	NP_001365690.1:p.Thr1483=	synonymous
NC_000011.10:g.121137971C>T
NC_000011.9:g.121008680C>T
NG_011633.1:g.40306C>T

... more HGVS ... less HGVS

Protein change

Other names

NM_005422.2(TECTA):c.3492C>T

Canonical SPDI

NC_000011.10:121137970:C:T

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.

0.00120 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00039

Exome Aggregation Consortium (ExAC) 0.00050

1000 Genomes Project 0.00120

1000 Genomes Project 30x 0.00125

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00138

The Genome Aggregation Database (gnomAD) 0.00138

Trans-Omics for Precision Medicine (TOPMed) 0.00144

Links

ClinGen: CA182519 dbSNP: rs144012985 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.
TBCEL-TECTA	-	-	-	GRCh38	-	1132
TECTA		-	-	GRCh38 GRCh37	6	1145

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.
not specified	Benign (1)	criteria provided, single submitter	Jun 16, 2016	RCV000155287.13
Autosomal recessive nonsyndromic hearing loss 21	Uncertain significance (1)	criteria provided, single submitter	Jan 13, 2018	RCV000352085.13
Autosomal dominant nonsyndromic hearing loss 12	Likely benign (1)	criteria provided, single submitter	Jan 13, 2018	RCV000401776.13
not provided	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Dec 2, 2023	RCV000906414.22
Nonsyndromic genetic hearing loss	Likely benign (1)	reviewed by expert panel	Feb 13, 2019	RCV000787985.9
TECTA-related disorder	Likely benign (1)	no assertion criteria provided	Mar 20, 2019	RCV003917524.2

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.
Likely benign (Feb 13, 2019)	reviewed by expert panel (ClinGen HL ACMG Specifications v1) Method: curation	Nonsyndromic genetic hearing loss (Autosomal recessive inheritance) Affected status: unknown Allele origin: germline	ClinGen Hearing Loss Variant Curation Expert Panel FDA Recognized Database Accession: SCV000927008.1 First in ClinVar: Jul 22, 2019 Last updated: Jul 22, 2019	Other databases https://erepo.clinicalgenome.org… https://erepo.clinicalgenome.org/evrepo/ui/interpretation/204ea045-9b19-4698-b5bd-11e5ab2a89f9 Comment: The filtering allele frequency of the c.3492C>T (p.Thr1164=) variant in the TECTA gene is 0.423% for African chromosomes by gnomAD (123/23960) with 95% CI), which … (more) The filtering allele frequency of the c.3492C>T (p.Thr1164=) variant in the TECTA gene is 0.423% for African chromosomes by gnomAD (123/23960) with 95% CI), which is a high enough frequency to be classified as likely benign based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BS1). The silent p.Thr1164= variant in TECTA is not predicted by MaxEntScan to impact splicing (BP7, BP4). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BS1, BP7, BP4. (less)
Benign (Jun 16, 2016)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000204973.5 First in ClinVar: Jan 31, 2015 Last updated: Apr 09, 2018	Comment: p.Thr1164Thr in Exon 10 of TECTA: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is … (more) p.Thr1164Thr in Exon 10 of TECTA: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 0.5% (52/10124) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broa dinstitute.org; dbSNP rs144012985). (less) Number of individuals with the variant: 4
Uncertain significance (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Autosomal recessive nonsyndromic hearing loss 21 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000368153.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
Likely benign (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Autosomal dominant nonsyndromic hearing loss 12 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000368154.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
Likely benign (Dec 16, 2020)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001779359.1 First in ClinVar: Aug 13, 2021 Last updated: Aug 13, 2021
Likely benign (Apr 13, 2021)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2021) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV002048721.1 First in ClinVar: Jan 08, 2022 Last updated: Jan 08, 2022
Benign (Dec 02, 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: SCV001051048.4 First in ClinVar: Dec 17, 2019 Last updated: Feb 14, 2024
Likely benign (Mar 20, 2019)	no assertion criteria provided Method: clinical testing	TECTA-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004732326.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Comment:

The filtering allele frequency of the c.3492C>T (p.Thr1164=) variant in the TECTA gene is 0.423% for African chromosomes by gnomAD (123/23960) with 95% CI), which is a high enough frequency to be classified as likely benign based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BS1). The silent p.Thr1164= variant in TECTA is not predicted by MaxEntScan to impact splicing (BP7, BP4). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BS1, BP7, BP4.

Comment:

p.Thr1164Thr in Exon 10 of TECTA: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 0.5% (52/10124) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broa dinstitute.org; dbSNP rs144012985).

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

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:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/204ea045-9b19-4698-b5bd-11e5ab2a89f9	-	-	-	-

Text-mined citations for rs144012985 ...

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 Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_005422.4(TECTA):c.3492C>T (p.Thr1164=)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs144012985 ...