11-121130065-T-C

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.2795T>C(p.Val932Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,613,878 control chromosomes in the GnomAD database, including 39,283 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V932L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.20 ( 3231 hom., cov: 33)

Exomes 𝑓: 0.22 ( 36052 hom. )

Consequence

TECTA
NM_005422.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 3.04

Publications

37 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 (MetaRNN=0.0015909076).

BP6

Variant 11-121130065-T-C is Benign according to our data. Variant chr11-121130065-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 45322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECTA	NM_005422.4 link	c.2795T>C	p.Val932Ala	missense_variant	Exon 10 of 24	ENST00000392793.6	NP_005413.2
TBCEL-TECTA	NM_001378761.1 link	c.3752T>C	p.Val1251Ala	missense_variant	Exon 16 of 30		NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
TECTA	ENST00000392793.6 link	c.2795T>C	p.Val932Ala	missense_variant	Exon 10 of 24	5	NM_005422.4	ENSP00000376543.1
TECTA	ENST00000264037.2 link	c.2795T>C	p.Val932Ala	missense_variant	Exon 9 of 23	1		ENSP00000264037.2
TECTA	ENST00000642222.1 link	c.2795T>C	p.Val932Ala	missense_variant	Exon 10 of 24			ENSP00000493855.1
TECTA	ENST00000645008.1 link	c.101T>C	p.Val34Ala	missense_variant	Exon 1 of 15			ENSP00000496274.1

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

31090

AN:

152012

Hom.:

3230

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.211

Gnomad EAS

AF:

0.234

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.189

GnomAD2 exomes

AF:

0.217

AC:

54409

AN:

251140

AF XY:

0.215

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.231

Gnomad ASJ exome

AF:

0.212

Gnomad EAS exome

AF:

0.245

Gnomad FIN exome

AF:

0.247

Gnomad NFE exome

AF:

0.213

Gnomad OTH exome

AF:

0.213

GnomAD4 exome

AF:

0.220

AC:

322267

AN:

1461748

Hom.:

36052

Cov.:

AF XY:

0.220

AC XY:

159741

AN XY:

727166

show subpopulations

African (AFR)

AF:

0.174

AC:

5809

AN:

33478

American (AMR)

AF:

0.229

AC:

10229

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

5631

AN:

26134

East Asian (EAS)

AF:

0.268

AC:

10633

AN:

39700

South Asian (SAS)

AF:

0.201

AC:

17322

AN:

86256

European-Finnish (FIN)

AF:

0.247

AC:

13164

AN:

53336

Middle Eastern (MID)

AF:

0.176

AC:

1012

AN:

5766

European-Non Finnish (NFE)

AF:

0.221

AC:

245730

AN:

1111972

Other (OTH)

AF:

0.211

AC:

12737

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

16773

33545

50318

67090

83863

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8512

17024

25536

34048

42560

<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:

0.204

AC:

31091

AN:

152130

Hom.:

3231

Cov.:

AF XY:

0.204

AC XY:

15171

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.171

AC:

7114

AN:

41512

American (AMR)

AF:

0.204

AC:

3126

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

732

AN:

3472

East Asian (EAS)

AF:

0.234

AC:

1213

AN:

5174

South Asian (SAS)

AF:

0.190

AC:

916

AN:

4822

European-Finnish (FIN)

AF:

0.243

AC:

2572

AN:

10580

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.219

AC:

14866

AN:

67968

Other (OTH)

AF:

0.190

AC:

401

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1304

2609

3913

5218

6522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

326

652

978

1304

1630

<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:

0.214

Hom.:

14307

Bravo

AF:

0.202

TwinsUK

AF:

0.221

AC:

820

ALSPAC

AF:

0.224

AC:

865

ESP6500AA

AF:

0.175

AC:

771

ESP6500EA

AF:

0.210

AC:

1809

ExAC

AF:

0.214

AC:

25963

Asia WGS

AF:

0.213

AC:

740

AN:

3478

EpiCase

AF:

0.203

EpiControl

AF:

0.196

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:10

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

Val932Ala in Exon 09 of TECTA: This variant is not expected to have clinical sig nificance because it has been identified in 21.0% (1477/7020) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs520805).

Dec 16, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:3

Mar 03, 2015

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Autosomal recessive nonsyndromic hearing loss 21

Benign:2

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Autosomal dominant nonsyndromic hearing loss 12

Benign:2

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.11

T;.;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.061

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.0

.;T;T

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.92

L;.;L

PhyloP100

3.0

PrimateAI

Uncertain

0.67

PROVEAN

Benign

0.30

N;.;N

REVEL

Benign

0.12

Sift

Benign

0.54

T;.;T

Sift4G

Benign

0.73

T;.;T

Vest4

0.055

ClinPred

0.0050

GERP RS

4.7

PromoterAI

-0.14

Neutral

(source)

Varity_R

0.081

gMVP

0.71

Mutation Taster

=93/7

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