11-121125583-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005422.4(TECTA):c.1485A>G(p.Ala495Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 1,613,962 control chromosomes in the GnomAD database, including 407,423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 44421 hom., cov: 33)

Exomes 𝑓: 0.70 ( 363002 hom. )

Consequence

TECTA
NM_005422.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -9.07

Publications

25 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 11-121125583-A-G is Benign according to our data. Variant chr11-121125583-A-G is described in ClinVar as Benign. ClinVar VariationId is 45315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-9.07 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.921 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECTA	NM_005422.4 link	c.1485A>G	p.Ala495Ala	synonymous_variant	Exon 8 of 24	ENST00000392793.6	NP_005413.2	O75443
TBCEL-TECTA	NM_001378761.1 link	c.2442A>G	p.Ala814Ala	synonymous_variant	Exon 14 of 30		NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TECTA	ENST00000392793.6 link	c.1485A>G	p.Ala495Ala	synonymous_variant	Exon 8 of 24	5	NM_005422.4	ENSP00000376543.1	O75443
TECTA	ENST00000264037.2 link	c.1485A>G	p.Ala495Ala	synonymous_variant	Exon 7 of 23	1		ENSP00000264037.2	O75443
TECTA	ENST00000642222.1 link	c.1485A>G	p.Ala495Ala	synonymous_variant	Exon 8 of 24			ENSP00000493855.1	A0A2R8YDL0

Frequencies

GnomAD3 genomes

AF:

0.756

AC:

114975

AN:

152124

Hom.:

44364

Cov.:

show subpopulations

Gnomad AFR

AF:

0.928

Gnomad AMI

AF:

0.624

Gnomad AMR

AF:

0.672

Gnomad ASJ

AF:

0.611

Gnomad EAS

AF:

0.674

Gnomad SAS

AF:

0.734

Gnomad FIN

AF:

0.724

Gnomad MID

AF:

0.715

Gnomad NFE

AF:

0.692

Gnomad OTH

AF:

0.744

GnomAD2 exomes

AF:

0.703

AC:

176656

AN:

251170

AF XY:

0.704

show subpopulations

Gnomad AFR exome

AF:

0.936

Gnomad AMR exome

AF:

0.618

Gnomad ASJ exome

AF:

0.625

Gnomad EAS exome

AF:

0.674

Gnomad FIN exome

AF:

0.729

Gnomad NFE exome

AF:

0.697

Gnomad OTH exome

AF:

0.704

GnomAD4 exome

AF:

0.703

AC:

1027389

AN:

1461720

Hom.:

363002

Cov.:

AF XY:

0.704

AC XY:

511674

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.942

AC:

31525

AN:

33480

American (AMR)

AF:

0.623

AC:

27852

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.622

AC:

16253

AN:

26136

East Asian (EAS)

AF:

0.682

AC:

27060

AN:

39694

South Asian (SAS)

AF:

0.721

AC:

62205

AN:

86258

European-Finnish (FIN)

AF:

0.736

AC:

39230

AN:

53308

Middle Eastern (MID)

AF:

0.704

AC:

4062

AN:

5768

European-Non Finnish (NFE)

AF:

0.698

AC:

776418

AN:

1111964

Other (OTH)

AF:

0.708

AC:

42784

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

21033

42065

63098

84130

105163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19696

39392

59088

78784

98480

<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:

0.756

AC:

115079

AN:

152242

Hom.:

44421

Cov.:

AF XY:

0.755

AC XY:

56178

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.928

AC:

38577

AN:

41550

American (AMR)

AF:

0.672

AC:

10275

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.611

AC:

2119

AN:

3470

East Asian (EAS)

AF:

0.674

AC:

3489

AN:

5174

South Asian (SAS)

AF:

0.734

AC:

3536

AN:

4820

European-Finnish (FIN)

AF:

0.724

AC:

7681

AN:

10608

Middle Eastern (MID)

AF:

0.721

AC:

212

AN:

294

European-Non Finnish (NFE)

AF:

0.692

AC:

47056

AN:

68004

Other (OTH)

AF:

0.742

AC:

1565

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1409

2819

4228

5638

7047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

842

1684

2526

3368

4210

<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:

0.707

Hom.:

25127

Bravo

AF:

0.757

Asia WGS

AF:

0.725

AC:

2522

AN:

3478

EpiCase

AF:

0.689

EpiControl

AF:

0.690

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

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

Ala495Ala in Exon 07 of TECTA: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 31.0% (2176/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs536069). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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. -

Autosomal recessive nonsyndromic hearing loss 21

Benign:2

Jan 13, 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. -

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: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

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.034

(source)

DANN

Benign

0.22

PhyloP100

-9.1

Mutation Taster

=83/17

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