rs612969

Positions:

chr11-121118626-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

This summary comes from the ClinGen Evidence Repository: The filtering allele frequency of the p.Arg317Gly variant in the TECTA gene is 67.5% (16434/24006) of African chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal dominant and autosomal recessive hearing loss variants (BA1). LINK:https://erepo.genome.network/evrepo/ui/classification/CA136018/MONDO:0019497/005

Frequency

Genomes: 𝑓 0.48 ( 18608 hom., cov: 31)

Exomes 𝑓: 0.42 ( 130676 hom. )

Consequence

TECTA
NM_005422.4 missense

Scores

Clinical Significance

Benign reviewed by expert panel B:10

Conservation

PhyloP100: 4.96

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 -8 ACMG points.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TECTA	NM_005422.4 linkuse as main transcript	c.1111A>G	p.Arg371Gly	missense_variant	7/24	ENST00000392793.6	NP_005413.2
TBCEL-TECTA	NM_001378761.1 linkuse as main transcript	c.2068A>G	p.Arg690Gly	missense_variant	13/30		NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TECTA	ENST00000392793.6 linkuse as main transcript	c.1111A>G	p.Arg371Gly	missense_variant	7/24	5	NM_005422.4	ENSP00000376543	P4
TECTA	ENST00000264037.2 linkuse as main transcript	c.1111A>G	p.Arg371Gly	missense_variant	6/23	1		ENSP00000264037	P4
TECTA	ENST00000642222.1 linkuse as main transcript	c.1111A>G	p.Arg371Gly	missense_variant	7/24			ENSP00000493855	A1

Frequencies

GnomAD3 genomes

AF:

0.475

AC:

72144

AN:

151848

Hom.:

18595

Cov.:

show subpopulations

Gnomad AFR

AF:

0.678

Gnomad AMI

AF:

0.257

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.366

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.317

Gnomad FIN

AF:

0.460

Gnomad MID

AF:

0.309

Gnomad NFE

AF:

0.420

Gnomad OTH

AF:

0.438

GnomAD3 exomes

AF:

0.398

AC:

99962

AN:

251444

Hom.:

21085

AF XY:

0.391

AC XY:

53154

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.686

Gnomad AMR exome

AF:

0.332

Gnomad ASJ exome

AF:

0.362

Gnomad EAS exome

AF:

0.249

Gnomad SAS exome

AF:

0.316

Gnomad FIN exome

AF:

0.464

Gnomad NFE exome

AF:

0.413

Gnomad OTH exome

AF:

0.386

GnomAD4 exome

AF:

0.418

AC:

610985

AN:

1461832

Hom.:

130676

Cov.:

AF XY:

0.413

AC XY:

300683

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.695

Gnomad4 AMR exome

AF:

0.338

Gnomad4 ASJ exome

AF:

0.364

Gnomad4 EAS exome

AF:

0.271

Gnomad4 SAS exome

AF:

0.318

Gnomad4 FIN exome

AF:

0.467

Gnomad4 NFE exome

AF:

0.426

Gnomad4 OTH exome

AF:

0.406

GnomAD4 genome

AF:

0.475

AC:

72204

AN:

151966

Hom.:

18608

Cov.:

AF XY:

0.468

AC XY:

34752

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.677

Gnomad4 AMR

AF:

0.361

Gnomad4 ASJ

AF:

0.366

Gnomad4 EAS

AF:

0.239

Gnomad4 SAS

AF:

0.315

Gnomad4 FIN

AF:

0.460

Gnomad4 NFE

AF:

0.420

Gnomad4 OTH

AF:

0.435

Alfa

AF:

0.421

Hom.:

30021

Bravo

AF:

0.479

TwinsUK

AF:

0.421

AC:

1561

ALSPAC

AF:

0.432

AC:

1664

ESP6500AA

AF:

0.663

AC:

2922

ESP6500EA

AF:

0.412

AC:

3545

ExAC

AF:

0.403

AC:

48890

Asia WGS

AF:

0.299

AC:

1040

AN:

3478

EpiCase

AF:

0.398

EpiControl

AF:

0.394

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2017	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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Arg371Gly in Exon 06 of TECTA: This variant is not expected to have clinical sig nificance because it has been identified in 41.0% (2877/7020) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs612969). -
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	Illumina Laboratory Services, Illumina	Jan 12, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 10, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal dominant nonsyndromic hearing loss 12

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 10, 2021	- -

Nonsyndromic genetic hearing loss

Benign:1

Benign, reviewed by expert panel

curation

ClinGen Hearing Loss Variant Curation Expert Panel

Sep 28, 2018

The filtering allele frequency of the p.Arg317Gly variant in the TECTA gene is 67.5% (16434/24006) of African chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org; calculated by using inverse allele frequency at https://www.cardiodb.org/allelefrequencyapp/), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal dominant and autosomal recessive hearing loss variants (BA1). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.33

DEOGEN2

Benign

0.094

T;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.037

.;T;T

MetaRNN

Benign

0.0000034

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-2.5

N;.;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.45

PROVEAN

Benign

6.1

N;.;N

REVEL

Benign

0.16

Sift

Benign

1.0

T;.;T

Sift4G

Benign

1.0

T;.;T

Polyphen

0.0

B;.;B

Vest4

0.041

MPC

0.41

ClinPred

0.0020

GERP RS

3.9

Varity_R

0.081

gMVP

0.53

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