rs144012985
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1
The NM_005422.4(TECTA):c.3492C>T(p.Thr1164=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,613,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★★).
Frequency
Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 0 hom. )
Consequence
TECTA
NM_005422.4 synonymous
NM_005422.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.18
Genes affected
TECTA (HGNC:11720): (tectorin alpha) The tectorial membrane is an extracellular matrix of the inner ear that contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia, and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals. Alpha-tectorin is one of the major noncollagenous components of the tectorial membrane. Mutations in the TECTA gene have been shown to be responsible for autosomal dominant nonsyndromic hearing impairment and a recessive form of sensorineural pre-lingual non-syndromic deafness. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
Variant 11-121137971-C-T is Benign according to our data. Variant chr11-121137971-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 178539.Status of the report is reviewed_by_expert_panel, 3 stars.
BP7
?
Synonymous conserved (PhyloP=-1.17 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00129 (197/152234) while in subpopulation AFR AF= 0.00448 (186/41528). AF 95% confidence interval is 0.00395. There are 0 homozygotes in gnomad4. There are 97 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TECTA | NM_005422.4 | c.3492C>T | p.Thr1164= | synonymous_variant | 11/24 | ENST00000392793.6 | |
TBCEL-TECTA | NM_001378761.1 | c.4449C>T | p.Thr1483= | synonymous_variant | 17/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TECTA | ENST00000392793.6 | c.3492C>T | p.Thr1164= | synonymous_variant | 11/24 | 5 | NM_005422.4 | P4 | |
TECTA | ENST00000264037.2 | c.3492C>T | p.Thr1164= | synonymous_variant | 10/23 | 1 | P4 | ||
TECTA | ENST00000642222.1 | c.3492C>T | p.Thr1164= | synonymous_variant | 11/24 | A1 | |||
TECTA | ENST00000645008.1 | c.801C>T | p.Thr267= | synonymous_variant | 2/15 |
Frequencies
GnomAD3 genomes ? AF: 0.00128 AC: 194AN: 152116Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000393 AC: 98AN: 249512Hom.: 0 AF XY: 0.000311 AC XY: 42AN XY: 134978
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GnomAD4 exome AF: 0.000159 AC: 232AN: 1460800Hom.: 0 Cov.: 32 AF XY: 0.000156 AC XY: 113AN XY: 726458
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ClinVar
Significance: Likely benign
Submissions summary: Uncertain:1Benign:7
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 02, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Apr 13, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 16, 2020 | - - |
Autosomal recessive nonsyndromic hearing loss 21 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 16, 2016 | 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). - |
Nonsyndromic genetic hearing loss Benign:1
Likely benign, reviewed by expert panel | curation | ClinGen Hearing Loss Variant Curation Expert Panel | Feb 13, 2019 | 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. - |
Autosomal dominant nonsyndromic hearing loss 12 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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. - |
TECTA-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 20, 2019 | 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). - |
Computational scores
Source:
Name
Calibrated prediction
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at