11-121130065-T-C

Position:

chr11-121130065-T-C

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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 Uncertain significance.

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:9

Conservation

PhyloP100: 3.04

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:):

TBCEL-TECTA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 45322.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-121130065-T-C is described in Lovd as [Benign].

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/exons	MANE	UniProt
TECTA	NM_005422.4 linkuse as main transcript	c.2795T>C	p.Val932Ala	missense_variant	10/24	ENST00000392793.6
TBCEL-TECTA	NM_001378761.1 linkuse as main transcript	c.3752T>C	p.Val1251Ala	missense_variant	16/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TECTA	ENST00000392793.6 linkuse as main transcript	c.2795T>C	p.Val932Ala	missense_variant	10/24	5	NM_005422.4	P4
TECTA	ENST00000264037.2 linkuse as main transcript	c.2795T>C	p.Val932Ala	missense_variant	9/23	1		P4
TECTA	ENST00000642222.1 linkuse as main transcript	c.2795T>C	p.Val932Ala	missense_variant	10/24			A1
TECTA	ENST00000645008.1 linkuse as main transcript	c.104T>C	p.Val35Ala	missense_variant	1/15

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

GnomAD3 exomes

AF:

0.217

AC:

54409

AN:

251140

Hom.:

6013

AF XY:

0.215

AC XY:

29122

AN XY:

135736

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 SAS exome

AF:

0.200

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

Gnomad4 AFR exome

AF:

0.174

Gnomad4 AMR exome

AF:

0.229

Gnomad4 ASJ exome

AF:

0.215

Gnomad4 EAS exome

AF:

0.268

Gnomad4 SAS exome

AF:

0.201

Gnomad4 FIN exome

AF:

0.247

Gnomad4 NFE exome

AF:

0.221

Gnomad4 OTH exome

AF:

0.211

GnomAD4 genome

AF:

0.204

AC:

31091

AN:

152130

Hom.:

3231

Cov.:

AF XY:

0.204

AC XY:

15171

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.171

Gnomad4 AMR

AF:

0.204

Gnomad4 ASJ

AF:

0.211

Gnomad4 EAS

AF:

0.234

Gnomad4 SAS

AF:

0.190

Gnomad4 FIN

AF:

0.243

Gnomad4 NFE

AF:

0.219

Gnomad4 OTH

AF:

0.190

Alfa

AF:

0.213

Hom.:

8092

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:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 16, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	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). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Autosomal recessive nonsyndromic hearing loss 21

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 10, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	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. -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Autosomal dominant nonsyndromic hearing loss 12

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 10, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	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. -

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

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

0.58

.;T;T

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.92

L;.;L

MutationTaster

Benign

0.22

P;P

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

Polyphen

0.0030

B;.;B

Vest4

0.055

MPC

0.39

ClinPred

0.0050

GERP RS

4.7

Varity_R

0.081

gMVP

0.71

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over