rs35507522

Positions:

chr11-121102721-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005422.4(TECTA):c.56A>G(p.Gln19Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 1,613,160 control chromosomes in the GnomAD database, including 624 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 (★★).

Frequency

Genomes: 𝑓 0.038 ( 270 hom., cov: 32)

Exomes 𝑓: 0.012 ( 354 hom. )

Consequence

TECTA
NM_005422.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.0510

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:

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=0.0012865365).

BP6

Variant 11-121102721-A-G is Benign according to our data. Variant chr11-121102721-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 45339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-121102721-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TECTA	NM_005422.4 linkuse as main transcript	c.56A>G	p.Gln19Arg	missense_variant	2/24	ENST00000392793.6	NP_005413.2	O75443
TBCEL-TECTA	NM_001378761.1 linkuse as main transcript	c.1013A>G	p.Gln338Arg	missense_variant	8/30		NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6 linkuse as main transcript	c.56A>G	p.Gln19Arg	missense_variant	2/24	5	NM_005422.4	ENSP00000376543.1		O75443
TBCEL-TECTA	ENST00000645041.1 linkuse as main transcript	c.965A>G	p.Gln322Arg	missense_variant	7/10			ENSP00000496315.1		A0A2R8YFB7

Frequencies

GnomAD3 genomes

AF:

0.0375

AC:

5710

AN:

152142

Hom.:

269

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.0176

Gnomad AMR

AF:

0.0177

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0313

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.00891

Gnomad OTH

AF:

0.0310

GnomAD3 exomes

AF:

0.0178

AC:

4474

AN:

251098

Hom.:

142

AF XY:

0.0177

AC XY:

2408

AN XY:

135684

show subpopulations

Gnomad AFR exome

AF:

0.115

Gnomad AMR exome

AF:

0.0103

Gnomad ASJ exome

AF:

0.0181

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0301

Gnomad FIN exome

AF:

0.000831

Gnomad NFE exome

AF:

0.00914

Gnomad OTH exome

AF:

0.0140

GnomAD4 exome

AF:

0.0124

AC:

18135

AN:

1460900

Hom.:

354

Cov.:

AF XY:

0.0130

AC XY:

9474

AN XY:

726832

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.0110

Gnomad4 ASJ exome

AF:

0.0179

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0300

Gnomad4 FIN exome

AF:

0.000599

Gnomad4 NFE exome

AF:

0.00840

Gnomad4 OTH exome

AF:

0.0182

GnomAD4 genome

AF:

0.0376

AC:

5728

AN:

152260

Hom.:

270

Cov.:

AF XY:

0.0365

AC XY:

2716

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.109

Gnomad4 AMR

AF:

0.0177

Gnomad4 ASJ

AF:

0.0173

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0321

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.00891

Gnomad4 OTH

AF:

0.0307

Alfa

AF:

0.0157

Hom.:

118

Bravo

AF:

0.0427

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.102

AC:

451

ESP6500EA

AF:

0.00954

AC:

ExAC

AF:

0.0201

AC:

2439

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.0111

EpiControl

AF:

0.0114

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 23, 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	Gln19Arg in Exon 01 of TECTA: This variant is not expected to have clinical sign ificance because it has been identified in 10.3% (386/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs35507522). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 12, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal recessive nonsyndromic hearing loss 21

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Autosomal dominant nonsyndromic hearing loss 12

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.75

CADD

Benign

4.6

DANN

Benign

0.39

DEOGEN2

Benign

0.098

.;T;.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0045

LIST_S2

Benign

0.12

T;.;T;T

MetaRNN

Benign

0.0013

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

.;N;.;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.45

.;N;.;N

REVEL

Benign

0.068

Sift

Benign

1.0

.;T;.;T

Sift4G

Benign

1.0

.;T;.;T

Polyphen

0.0

.;B;.;B

Vest4

0.057, 0.097

MPC

0.35

ClinPred

0.0028

GERP RS

-1.1

Varity_R

0.043

gMVP

0.47

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