11-121130075-T-C

Variant names:

• chr11-121130075-T-C
• rs586473
• NM_005422.4:c.2805T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005422.4(TECTA):​c.2805T>C​(p.Tyr935Tyr) variant causes a synonymous change. The variant allele was found at a frequency of 0.702 in 1,613,820 control chromosomes in the GnomAD database, including 399,356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (41683 hom., cov: 32)
  • Exomes 𝑓: 0.70 (357673 hom.)
• Consequence: TECTA NM_005422.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: 4.09

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]

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 11-121130075-T-C is Benign according to our data. Variant chr11-121130075-T-C is described in ClinVar as [Benign]. Clinvar id is 45323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-121130075-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECTA	NM_005422.4	c.2805T>C	p.Tyr935Tyr	synonymous_variant	Exon 10 of 24	ENST00000392793.6	NP_005413.2
TBCEL-TECTA	NM_001378761.1	c.3762T>C	p.Tyr1254Tyr	synonymous_variant	Exon 16 of 30		NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6	c.2805T>C	p.Tyr935Tyr	synonymous_variant	Exon 10 of 24	5	NM_005422.4	ENSP00000376543.1
TECTA	ENST00000264037.2	c.2805T>C	p.Tyr935Tyr	synonymous_variant	Exon 9 of 23	1		ENSP00000264037.2
TECTA	ENST00000642222.1	c.2805T>C	p.Tyr935Tyr	synonymous_variant	Exon 10 of 24			ENSP00000493855.1
TECTA	ENST00000645008.1	c.111T>C	p.Tyr37Tyr	synonymous_variant	Exon 1 of 15			ENSP00000496274.1

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111771 AN: 151972 Hom.: 41644 Cov.: 32

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.732

GnomAD3 exomes AF: 0.697 AC: 174979 AN: 251196 Hom.: 61545 AF XY: 0.698 AC XY: 94816 AN XY: 135744

Gnomad AFR exome AF: 0.869

Gnomad AMR exome AF: 0.612

Gnomad ASJ exome AF: 0.624

Gnomad EAS exome AF: 0.675

Gnomad SAS exome AF: 0.724

Gnomad FIN exome AF: 0.728

Gnomad NFE exome AF: 0.694

Gnomad OTH exome AF: 0.700

GnomAD4 exome AF: 0.698 AC: 1020545 AN: 1461730 Hom.: 357673 Cov.: 87 AF XY: 0.699 AC XY: 508448 AN XY: 727152

Gnomad4 AFR exome AF: 0.875

Gnomad4 AMR exome AF: 0.617

Gnomad4 ASJ exome AF: 0.621

Gnomad4 EAS exome AF: 0.684

Gnomad4 SAS exome AF: 0.721

Gnomad4 FIN exome AF: 0.735

Gnomad4 NFE exome AF: 0.695

Gnomad4 OTH exome AF: 0.702

GnomAD4 genome AF: 0.735 AC: 111857 AN: 152090 Hom.: 41683 Cov.: 32 AF XY: 0.735 AC XY: 54653 AN XY: 74326

Gnomad4 AFR AF: 0.864

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.608

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.733

Gnomad4 FIN AF: 0.722

Gnomad4 NFE AF: 0.689

Gnomad4 OTH AF: 0.730

Alfa AF: 0.697 Hom.: 44597

Bravo AF: 0.734

Asia WGS AF: 0.722 AC: 2511 AN: 3478

EpiCase AF: 0.686

EpiControl AF: 0.686

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

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

Tyr935Tyr in Exon 09 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 31.4% (2201/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs586473). -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 16, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:3

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

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 21 Benign:2

Jan 12, 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

- -

Autosomal dominant nonsyndromic hearing loss 12 Benign:2

Jan 12, 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	10
DANN	Benign	0.58

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

Other links and lift over

dbSNP: rs586473; hg19: chr11-121000784; COSMIC: COSV50691860;