11-121146129-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005422.4(TECTA):c.4105+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,602,936 control chromosomes in the GnomAD database, including 38,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5910 hom., cov: 33)

Exomes 𝑓: 0.20 ( 32215 hom. )

Consequence

TECTA
NM_005422.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0420

Publications

7 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 11-121146129-C-T is Benign according to our data. Variant chr11-121146129-C-T is described in ClinVar as Benign. ClinVar VariationId is 45330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECTA	NM_005422.4 link	c.4105+13C>T		intron_variant	Intron 12 of 23	ENST00000392793.6	NP_005413.2	O75443
TBCEL-TECTA	NM_001378761.1 link	c.5062+13C>T		intron_variant	Intron 18 of 29		NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6 link	c.4105+13C>T		intron_variant	Intron 12 of 23	5	NM_005422.4	ENSP00000376543.1		O75443

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38333

AN:

152104

Hom.:

5903

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.157

Gnomad ASJ

AF:

0.155

Gnomad EAS

AF:

0.00442

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.215

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.245

GnomAD2 exomes

AF:

0.180

AC:

42174

AN:

234122

AF XY:

0.179

show subpopulations

Gnomad AFR exome

AF:

0.442

Gnomad AMR exome

AF:

0.103

Gnomad ASJ exome

AF:

0.153

Gnomad EAS exome

AF:

0.00243

Gnomad FIN exome

AF:

0.226

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.178

GnomAD4 exome

AF:

0.202

AC:

292806

AN:

1450714

Hom.:

32215

Cov.:

AF XY:

0.199

AC XY:

143851

AN XY:

722082

show subpopulations

African (AFR)

AF:

0.440

AC:

14720

AN:

33450

American (AMR)

AF:

0.110

AC:

4934

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

3954

AN:

26134

East Asian (EAS)

AF:

0.00139

AC:

AN:

39692

South Asian (SAS)

AF:

0.137

AC:

11772

AN:

86178

European-Finnish (FIN)

AF:

0.221

AC:

9630

AN:

43562

Middle Eastern (MID)

AF:

0.173

AC:

920

AN:

5314

European-Non Finnish (NFE)

AF:

0.211

AC:

234970

AN:

1111404

Other (OTH)

AF:

0.197

AC:

11851

AN:

60274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

12673

25347

38020

50694

63367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8076

16152

24228

32304

40380

<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:

0.252

AC:

38354

AN:

152222

Hom.:

5910

Cov.:

AF XY:

0.245

AC XY:

18254

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.424

AC:

17620

AN:

41524

American (AMR)

AF:

0.157

AC:

2396

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

537

AN:

3472

East Asian (EAS)

AF:

0.00424

AC:

AN:

5188

South Asian (SAS)

AF:

0.146

AC:

703

AN:

4828

European-Finnish (FIN)

AF:

0.215

AC:

2274

AN:

10592

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.207

AC:

14082

AN:

68000

Other (OTH)

AF:

0.242

AC:

511

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1387

2774

4160

5547

6934

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

376

752

1128

1504

1880

<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:

0.218

Hom.:

1136

Bravo

AF:

0.256

Asia WGS

AF:

0.0850

AC:

295

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 22, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

4105+13C>T in Intron 11 of TECTA: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence and has been identified in 39.1% (1443/3688) of African American chromosom es from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs. washington.edu/EVS; dbSNP rs7130952). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 21

Benign:1

Jan 12, 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 12, 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

-0.83

CADD

Benign

0.77

(source)

DANN

Benign

0.51

PhyloP100

-0.042

Mutation Taster

=100/0

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