chr11-121137783-G-A

Position:

• chr11-121137783-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005422.4(TECTA):​c.3304G>A​(p.Val1102Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000458 in 1,614,104 control chromosomes in the GnomAD database, including 5 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (4 hom.)
• Consequence: TECTA NM_005422.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 5.74

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 (MetaRNN=0.0072684586).
• BP6: Variant 11-121137783-G-A is Benign according to our data. Variant chr11-121137783-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 45326.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00229 (348/152266) while in subpopulation AFR AF= 0.00811 (337/41548). AF 95% confidence interval is 0.0074. There are 1 homozygotes in gnomad4. There are 158 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TECTA	NM_005422.4	c.3304G>A	p.Val1102Ile	missense_variant	11/24	ENST00000392793.6	NP_005413.2
TBCEL-TECTA	NM_001378761.1	c.4261G>A	p.Val1421Ile	missense_variant	17/30		NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6	c.3304G>A	p.Val1102Ile	missense_variant	11/24	5	NM_005422.4	ENSP00000376543.1
TECTA	ENST00000264037.2	c.3304G>A	p.Val1102Ile	missense_variant	10/23	1		ENSP00000264037.2
TECTA	ENST00000642222.1	c.3304G>A	p.Val1102Ile	missense_variant	11/24			ENSP00000493855.1
TECTA	ENST00000645008.1	c.610G>A	p.Val204Ile	missense_variant	2/15			ENSP00000496274.1

Frequencies

GnomAD3 genomes AF: 0.00229 AC: 348 AN: 152148 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00813

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000609 AC: 153 AN: 251164 Hom.: 0 AF XY: 0.000427 AC XY: 58 AN XY: 135722

Gnomad AFR exome AF: 0.00886

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000268 AC: 392 AN: 1461838 Hom.: 4 Cov.: 32 AF XY: 0.000243 AC XY: 177 AN XY: 727210

Gnomad4 AFR exome AF: 0.00998

Gnomad4 AMR exome AF: 0.000157

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000989

Gnomad4 OTH exome AF: 0.000580

GnomAD4 genome AF: 0.00229 AC: 348 AN: 152266 Hom.: 1 Cov.: 32 AF XY: 0.00212 AC XY: 158 AN XY: 74442

Gnomad4 AFR AF: 0.00811

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000509 Hom.: 0

Bravo AF: 0.00260

ESP6500AA AF: 0.00840 AC: 37

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000717 AC: 87

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 14, 2020	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 28, 2023	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 04, 2015

p.Val1102Ile in exon 10 of TECTA: This variant is not expected to have clinical significance because it has been identified in 0.8% (85/10382) of African chromo somes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs34658230). -

TECTA-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 05, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T;.;T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.052
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.74	.;T;T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.0073	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.6	L;.;L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.50	N;.;N
REVEL	Benign	0.13
Sift	Benign	0.62	T;.;T
Sift4G	Benign	0.062	T;.;T
Polyphen		0.0020	B;.;B
Vest4		0.14
MVP		0.66
MPC		0.27
ClinPred		0.027	T
GERP RS		3.4
Varity_R		0.040
gMVP		0.39

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: rs34658230; hg19: chr11-121008492;