rs612969

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

40 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 -8 ACMG points.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECTA	NM_005422.4 link	c.1111A>G	p.Arg371Gly	missense_variant	Exon 7 of 24	ENST00000392793.6	NP_005413.2	O75443
TBCEL-TECTA	NM_001378761.1 link	c.2068A>G	p.Arg690Gly	missense_variant	Exon 13 of 30		NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TECTA	ENST00000392793.6 link	c.1111A>G	p.Arg371Gly	missense_variant	Exon 7 of 24	5	NM_005422.4	ENSP00000376543.1	O75443
TECTA	ENST00000264037.2 link	c.1111A>G	p.Arg371Gly	missense_variant	Exon 6 of 23	1		ENSP00000264037.2	O75443
TECTA	ENST00000642222.1 link	c.1111A>G	p.Arg371Gly	missense_variant	Exon 7 of 24			ENSP00000493855.1	A0A2R8YDL0

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

GnomAD2 exomes

AF:

0.398

AC:

99962

AN:

251444

AF XY:

0.391

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 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

African (AFR)

AF:

0.695

AC:

23257

AN:

33480

American (AMR)

AF:

0.338

AC:

15102

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.364

AC:

9509

AN:

26136

East Asian (EAS)

AF:

0.271

AC:

10747

AN:

39700

South Asian (SAS)

AF:

0.318

AC:

27462

AN:

86256

European-Finnish (FIN)

AF:

0.467

AC:

24933

AN:

53372

Middle Eastern (MID)

AF:

0.320

AC:

1844

AN:

5768

European-Non Finnish (NFE)

AF:

0.426

AC:

473581

AN:

1112000

Other (OTH)

AF:

0.406

AC:

24550

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

23488

46975

70463

93950

117438

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14458

28916

43374

57832

72290

<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:

0.475

AC:

72204

AN:

151966

Hom.:

18608

Cov.:

AF XY:

0.468

AC XY:

34752

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.677

AC:

28061

AN:

41428

American (AMR)

AF:

0.361

AC:

5513

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.366

AC:

1268

AN:

3468

East Asian (EAS)

AF:

0.239

AC:

1232

AN:

5154

South Asian (SAS)

AF:

0.315

AC:

1516

AN:

4814

European-Finnish (FIN)

AF:

0.460

AC:

4847

AN:

10542

Middle Eastern (MID)

AF:

0.329

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.420

AC:

28517

AN:

67974

Other (OTH)

AF:

0.435

AC:

920

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1816

3633

5449

7266

9082

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

622

1244

1866

2488

3110

<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:

0.431

Hom.:

44806

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

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. -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 21

Benign:2

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 12

Benign:2

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Nonsyndromic genetic hearing loss

Benign:1

Sep 28, 2018

ClinGen Hearing Loss Variant Curation Expert Panel

Significance:Benign

Review Status:reviewed by expert panel

Collection Method:curation

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

(source)

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

PhyloP100

5.0

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

Mutation Taster

=97/3

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