rs526433

Positions:

Variant summary

Our verdict is Benign. Variant got -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. 13/20 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

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:

TECTA (HGNC:):

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=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 id is 45336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-121162269-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
TECTA	NM_005422.4 linkuse as main transcript	c.5171G>A	p.Ser1724Asn	missense_variant	16/24	ENST00000392793.6	NP_005413.2	O75443
TBCEL-TECTA	NM_001378761.1 linkuse as main transcript	c.6113G>A	p.Ser2038Asn	missense_variant	22/30		NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6 linkuse as main transcript	c.5171G>A	p.Ser1724Asn	missense_variant	16/24	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

GnomAD3 exomes

AF:

0.993

AC:

249600

AN:

251398

Hom.:

123915

AF XY:

0.993

AC XY:

134939

AN XY:

135902

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 SAS exome

AF:

0.998

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

Gnomad4 AFR exome

AF:

0.999

Gnomad4 AMR exome

AF:

0.996

Gnomad4 ASJ exome

AF:

0.997

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.999

Gnomad4 FIN exome

AF:

0.992

Gnomad4 NFE exome

AF:

0.988

Gnomad4 OTH exome

AF:

0.991

GnomAD4 genome

AF:

0.993

AC:

151264

AN:

152406

Hom.:

75071

Cov.:

AF XY:

0.993

AC XY:

74014

AN XY:

74530

show subpopulations

Gnomad4 AFR

AF:

0.998

Gnomad4 AMR

AF:

0.994

Gnomad4 ASJ

AF:

0.996

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.997

Gnomad4 FIN

AF:

0.995

Gnomad4 NFE

AF:

0.988

Gnomad4 OTH

AF:

0.994

Alfa

AF:

0.989

Hom.:

94309

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

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	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). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 10, 2014	- -
Benign, criteria provided, single submitter	curation	SIB Swiss Institute of Bioinformatics	May 31, 2018	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. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Autosomal dominant nonsyndromic hearing loss 12

Benign:3

Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 10, 2021	- -

Autosomal recessive nonsyndromic hearing loss 21

Benign:2

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. -
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	-	- -

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

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

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

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