rs12275038

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005422.4(TECTA):c.4098G>A(p.Thr1366Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,607,516 control chromosomes in the GnomAD database, including 41,834 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 7227 hom., cov: 33)

Exomes 𝑓: 0.21 ( 34607 hom. )

Consequence

TECTA
NM_005422.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -4.01

Publications

11 publications found

Variant links:

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]

TECTA links:

TBCEL-TECTA (HGNC:54857): (TBCEL-TECTA readthrough) Predicted to enable alpha-tubulin binding activity. Predicted to be involved in microtubule cytoskeleton organization; post-chaperonin tubulin folding pathway; and tubulin complex assembly. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TBCEL-TECTA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 11-121146109-G-A is Benign according to our data. Variant chr11-121146109-G-A is described in ClinVar as Benign. ClinVar VariationId is 45329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECTA	NM_005422.4 link	c.4098G>A	p.Thr1366Thr	synonymous_variant	Exon 12 of 24	ENST00000392793.6	NP_005413.2	O75443
TBCEL-TECTA	NM_001378761.1 link	c.5055G>A	p.Thr1685Thr	synonymous_variant	Exon 18 of 30		NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6 link	c.4098G>A	p.Thr1366Thr	synonymous_variant	Exon 12 of 24	5	NM_005422.4	ENSP00000376543.1		O75443

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41570

AN:

152094

Hom.:

7215

Cov.:

show subpopulations

Gnomad AFR

AF:

0.489

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.171

Gnomad ASJ

AF:

0.162

Gnomad EAS

AF:

0.00461

Gnomad SAS

AF:

0.146

Gnomad FIN

AF:

0.215

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.267

GnomAD2 exomes

AF:

0.188

AC:

44846

AN:

238882

AF XY:

0.185

show subpopulations

Gnomad AFR exome

AF:

0.506

Gnomad AMR exome

AF:

0.108

Gnomad ASJ exome

AF:

0.159

Gnomad EAS exome

AF:

0.00248

Gnomad FIN exome

AF:

0.224

Gnomad NFE exome

AF:

0.212

Gnomad OTH exome

AF:

0.183

GnomAD4 exome

AF:

0.207

AC:

301908

AN:

1455304

Hom.:

34607

Cov.:

AF XY:

0.205

AC XY:

148106

AN XY:

724178

show subpopulations

African (AFR)

AF:

0.506

AC:

16940

AN:

33472

American (AMR)

AF:

0.117

AC:

5234

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.156

AC:

4086

AN:

26136

East Asian (EAS)

AF:

0.00139

AC:

AN:

39700

South Asian (SAS)

AF:

0.137

AC:

11795

AN:

86246

European-Finnish (FIN)

AF:

0.223

AC:

10514

AN:

47220

Middle Eastern (MID)

AF:

0.180

AC:

1018

AN:

5670

European-Non Finnish (NFE)

AF:

0.216

AC:

239879

AN:

1111812

Other (OTH)

AF:

0.205

AC:

12387

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

13547

27095

40642

54190

67737

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8248

16496

24744

32992

41240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.273

AC:

41616

AN:

152212

Hom.:

7227

Cov.:

AF XY:

0.266

AC XY:

19830

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.489

AC:

20307

AN:

41516

American (AMR)

AF:

0.171

AC:

2609

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.162

AC:

561

AN:

3472

East Asian (EAS)

AF:

0.00443

AC:

AN:

5190

South Asian (SAS)

AF:

0.146

AC:

707

AN:

4832

European-Finnish (FIN)

AF:

0.215

AC:

2280

AN:

10588

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.211

AC:

14360

AN:

68010

Other (OTH)

AF:

0.263

AC:

555

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1436

2872

4308

5744

7180

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

396

792

1188

1584

1980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.225

Hom.:

6735

Bravo

AF:

0.280

Asia WGS

AF:

0.0920

AC:

322

AN:

3478

EpiCase

AF:

0.208

EpiControl

AF:

0.210

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Thr1366Thr in Exon 11 of TECTA: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 46.4% (1724/3716) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs12275038). -

May 09, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autosomal recessive nonsyndromic hearing loss 21

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Autosomal dominant nonsyndromic hearing loss 12

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.069

(source)

DANN

Benign

0.48

PhyloP100

-4.0

Mutation Taster

=86/14

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over