rs681311

Positions:

• chr11-121105704-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005422.4(TECTA):​c.65-127G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,185,950 control chromosomes in the GnomAD database, including 95,064 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (10084 hom., cov: 33)
  • Exomes 𝑓: 0.40 (84980 hom.)
• Consequence: TECTA NM_005422.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.900

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]

TBCEL-TECTA (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-121105704-G-A is Benign according to our data. Variant chr11-121105704-G-A is described in ClinVar as [Benign]. Clinvar id is 1228332.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TECTA	NM_005422.4	c.65-127G>A		intron_variant		ENST00000392793.6	NP_005413.2
TBCEL-TECTA	NM_001378761.1	c.1022-127G>A		intron_variant			NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6	c.65-127G>A		intron_variant		5	NM_005422.4	ENSP00000376543.1
TBCEL-TECTA	ENST00000645041.1	c.974-127G>A		intron_variant				ENSP00000496315.1

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54813 AN: 152000 Hom.: 10084 Cov.: 33

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.371

GnomAD4 exome AF: 0.403 AC: 416689 AN: 1033832 Hom.: 84980 AF XY: 0.403 AC XY: 212210 AN XY: 526962

Gnomad4 AFR exome AF: 0.276

Gnomad4 AMR exome AF: 0.306

Gnomad4 ASJ exome AF: 0.426

Gnomad4 EAS exome AF: 0.373

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.330

Gnomad4 NFE exome AF: 0.420

Gnomad4 OTH exome AF: 0.392

GnomAD4 genome AF: 0.360 AC: 54827 AN: 152118 Hom.: 10084 Cov.: 33 AF XY: 0.356 AC XY: 26507 AN XY: 74362

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.373

Alfa AF: 0.371 Hom.: 1681

Bravo AF: 0.359

Asia WGS AF: 0.337 AC: 1175 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs681311; hg19: chr11-120976413; COSMIC: COSV50718534;