rs526433

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.5171G>A(p.Ser1724Asn) variant causes a missense change. The variant allele was found at a frequency of 0.99 in 1,614,034 control chromosomes in the GnomAD database, including 791,613 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.99 ( 75071 hom., cov: 36)

Exomes 𝑓: 0.99 ( 716542 hom. )

Consequence

TECTA
NM_005422.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: 5.89

Publications

36 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=6.168769E-7).

BP6

Variant 11-121162269-G-A is Benign according to our data. Variant chr11-121162269-G-A is described in ClinVar as Benign. ClinVar VariationId is 45336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECTA	NM_005422.4 link	c.5171G>A	p.Ser1724Asn	missense_variant	Exon 16 of 24	ENST00000392793.6	NP_005413.2	O75443
TBCEL-TECTA	NM_001378761.1 link	c.6113G>A	p.Ser2038Asn	missense_variant	Exon 22 of 30		NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6 link	c.5171G>A	p.Ser1724Asn	missense_variant	Exon 16 of 24	5	NM_005422.4	ENSP00000376543.1		O75443

Frequencies

GnomAD3 genomes

AF:

0.992

AC:

151145

AN:

152288

Hom.:

75011

Cov.:

show subpopulations

Gnomad AFR

AF:

0.998

Gnomad AMI

AF:

0.973

Gnomad AMR

AF:

0.994

Gnomad ASJ

AF:

0.996

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.997

Gnomad FIN

AF:

0.995

Gnomad MID

AF:

0.997

Gnomad NFE

AF:

0.988

Gnomad OTH

AF:

0.994

GnomAD2 exomes

AF:

0.993

AC:

249600

AN:

251398

AF XY:

0.993

show subpopulations

Gnomad AFR exome

AF:

0.999

Gnomad AMR exome

AF:

0.996

Gnomad ASJ exome

AF:

0.997

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.992

Gnomad NFE exome

AF:

0.988

Gnomad OTH exome

AF:

0.991

GnomAD4 exome

AF:

0.990

AC:

1447260

AN:

1461628

Hom.:

716542

Cov.:

AF XY:

0.990

AC XY:

720141

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.999

AC:

33439

AN:

33480

American (AMR)

AF:

0.996

AC:

44523

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.997

AC:

26046

AN:

26136

East Asian (EAS)

AF:

1.00

AC:

39700

AN:

39700

South Asian (SAS)

AF:

0.999

AC:

86133

AN:

86258

European-Finnish (FIN)

AF:

0.992

AC:

52727

AN:

53158

Middle Eastern (MID)

AF:

0.996

AC:

5744

AN:

5768

European-Non Finnish (NFE)

AF:

0.988

AC:

1099097

AN:

1112012

Other (OTH)

AF:

0.991

AC:

59851

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

983

1965

2948

3930

4913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21670

43340

65010

86680

108350

<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:

0.993

AC:

151264

AN:

152406

Hom.:

75071

Cov.:

AF XY:

0.993

AC XY:

74014

AN XY:

74530

show subpopulations

African (AFR)

AF:

0.998

AC:

41502

AN:

41602

American (AMR)

AF:

0.994

AC:

15223

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.996

AC:

3458

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5189

AN:

5190

South Asian (SAS)

AF:

0.997

AC:

4817

AN:

4830

European-Finnish (FIN)

AF:

0.995

AC:

10577

AN:

10630

Middle Eastern (MID)

AF:

0.997

AC:

293

AN:

294

European-Non Finnish (NFE)

AF:

0.988

AC:

67217

AN:

68048

Other (OTH)

AF:

0.994

AC:

2101

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

132

198

264

330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

916

1832

2748

3664

4580

<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:

0.990

Hom.:

136014

Bravo

AF:

0.993

TwinsUK

AF:

0.989

AC:

3667

ALSPAC

AF:

0.988

AC:

3808

ESP6500AA

AF:

0.998

AC:

4395

ESP6500EA

AF:

0.989

AC:

8506

ExAC

AF:

0.993

AC:

120520

Asia WGS

AF:

0.999

AC:

3473

AN:

3478

EpiCase

AF:

0.988

EpiControl

AF:

0.988

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

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. -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Dec 10, 2014

Eurofins Ntd Llc (ga)

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

Ser1724Asn in Exon 15 of TECTA: This variant is not expected to have clinical si gnificance because it has been identified in 1.1% (75/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs526433). -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 31, 2018

SIB Swiss Institute of Bioinformatics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

This variant is interpreted as a Benign - Stand Alone. The following ACMG Tag(s) were applied: BA1 => Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. -

Autosomal dominant nonsyndromic hearing loss 12

Benign:3

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

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:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.27

DEOGEN2

Benign

0.075

T;.;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.23

.;T;T

MetaRNN

Benign

6.2e-7

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.52

N;.;N

PhyloP100

5.9

PrimateAI

Uncertain

0.67

PROVEAN

Benign

0.92

N;.;N

REVEL

Benign

0.27

Sift

Benign

1.0

T;.;T

Sift4G

Benign

1.0

T;.;T

Polyphen

0.0

B;.;B

Vest4

0.19

MPC

0.30

ClinPred

0.0046

GERP RS

5.5

Varity_R

0.079

gMVP

0.54

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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