11-121146129-C-T

Position:

chr11-121146129-C-T

Variant summary

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

The NM_005422.4(TECTA):c.4105+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 1,602,936 control chromosomes in the GnomAD database, including 38,125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5910 hom., cov: 33)

Exomes 𝑓: 0.20 ( 32215 hom. )

Consequence

TECTA
NM_005422.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.0420

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 (BayesDel_noAF=-0.83).

BP6

Variant 11-121146129-C-T is Benign according to our data. Variant chr11-121146129-C-T is described in ClinVar as [Benign]. Clinvar id is 45330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-121146129-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 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.4105+13C>T		intron_variant		ENST00000392793.6	NP_005413.2	O75443
TBCEL-TECTA	NM_001378761.1 linkuse as main transcript	c.5062+13C>T		intron_variant			NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6 linkuse as main transcript	c.4105+13C>T		intron_variant		5	NM_005422.4	ENSP00000376543.1		O75443

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38333

AN:

152104

Hom.:

5903

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.157

Gnomad ASJ

AF:

0.155

Gnomad EAS

AF:

0.00442

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.215

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.245

GnomAD3 exomes

AF:

0.180

AC:

42174

AN:

234122

Hom.:

4847

AF XY:

0.179

AC XY:

23079

AN XY:

128618

show subpopulations

Gnomad AFR exome

AF:

0.442

Gnomad AMR exome

AF:

0.103

Gnomad ASJ exome

AF:

0.153

Gnomad EAS exome

AF:

0.00243

Gnomad SAS exome

AF:

0.136

Gnomad FIN exome

AF:

0.226

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.178

GnomAD4 exome

AF:

0.202

AC:

292806

AN:

1450714

Hom.:

32215

Cov.:

AF XY:

0.199

AC XY:

143851

AN XY:

722082

show subpopulations

Gnomad4 AFR exome

AF:

0.440

Gnomad4 AMR exome

AF:

0.110

Gnomad4 ASJ exome

AF:

0.151

Gnomad4 EAS exome

AF:

0.00139

Gnomad4 SAS exome

AF:

0.137

Gnomad4 FIN exome

AF:

0.221

Gnomad4 NFE exome

AF:

0.211

Gnomad4 OTH exome

AF:

0.197

GnomAD4 genome

AF:

0.252

AC:

38354

AN:

152222

Hom.:

5910

Cov.:

AF XY:

0.245

AC XY:

18254

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.424

Gnomad4 AMR

AF:

0.157

Gnomad4 ASJ

AF:

0.155

Gnomad4 EAS

AF:

0.00424

Gnomad4 SAS

AF:

0.146

Gnomad4 FIN

AF:

0.215

Gnomad4 NFE

AF:

0.207

Gnomad4 OTH

AF:

0.242

Alfa

AF:

0.213

Hom.:

1047

Bravo

AF:

0.256

Asia WGS

AF:

0.0850

AC:

295

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	4105+13C>T in Intron 11 of TECTA: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence and has been identified in 39.1% (1443/3688) of African American chromosom es from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs. washington.edu/EVS; dbSNP rs7130952). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Autosomal recessive nonsyndromic hearing loss 21

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Autosomal dominant nonsyndromic hearing loss 12

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.77

DANN

Benign

0.51

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