chr11-121128233-C-T

Variant names:

• chr11-121128233-C-T
• rs10502247
• NM_005422.4:c.2256C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_005422.4(TECTA):​c.2256C>T​(p.Ile752Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,601,288 control chromosomes in the GnomAD database, including 68,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5753 hom., cov: 32)
  • Exomes 𝑓: 0.29 (62686 hom.)
• Consequence: TECTA NM_005422.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -0.546
• Publications: 24 publications found

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

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 11-121128233-C-T is Benign according to our data. Variant chr11-121128233-C-T is described in ClinVar as Benign. ClinVar VariationId is 45319.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.546 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005422.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECTA	NM_005422.4	MANE Select	c.2256C>T	p.Ile752Ile	synonymous	Exon 9 of 24	NP_005413.2	O75443
	TBCEL-TECTA	NM_001378761.1		c.3213C>T	p.Ile1071Ile	synonymous	Exon 15 of 30	NP_001365690.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECTA	ENST00000392793.6	TSL:5 MANE Select	c.2256C>T	p.Ile752Ile	synonymous	Exon 9 of 24	ENSP00000376543.1	O75443
	TECTA	ENST00000264037.2	TSL:1	c.2256C>T	p.Ile752Ile	synonymous	Exon 8 of 23	ENSP00000264037.2	O75443
	TECTA	ENST00000642222.1		c.2256C>T	p.Ile752Ile	synonymous	Exon 9 of 24	ENSP00000493855.1	A0A2R8YDL0

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40605 AN: 151984 Hom.: 5752 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.301

GnomAD2 exomes AF: 0.307 AC: 74163 AN: 241670 AF XY: 0.315

Gnomad AFR exome AF: 0.186

Gnomad AMR exome AF: 0.283

Gnomad ASJ exome AF: 0.266

Gnomad EAS exome AF: 0.425

Gnomad FIN exome AF: 0.274

Gnomad NFE exome AF: 0.291

Gnomad OTH exome AF: 0.322

GnomAD4 exome AF: 0.290 AC: 420029 AN: 1449186 Hom.: 62686 Cov.: 67 AF XY: 0.295 AC XY: 212889 AN XY: 721308

African (AFR) AF: 0.184 AC: 6152 AN: 33478

American (AMR) AF: 0.282 AC: 12614 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 6818 AN: 26134

East Asian (EAS) AF: 0.411 AC: 16312 AN: 39696

South Asian (SAS) AF: 0.404 AC: 34807 AN: 86258

European-Finnish (FIN) AF: 0.274 AC: 11198 AN: 40880

Middle Eastern (MID) AF: 0.381 AC: 2198 AN: 5768

European-Non Finnish (NFE) AF: 0.280 AC: 311567 AN: 1111936

Other (OTH) AF: 0.304 AC: 18363 AN: 60318

GnomAD4 genome AF: 0.267 AC: 40630 AN: 152102 Hom.: 5753 Cov.: 32 AF XY: 0.273 AC XY: 20299 AN XY: 74332

African (AFR) AF: 0.191 AC: 7931 AN: 41516

American (AMR) AF: 0.300 AC: 4588 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 862 AN: 3470

East Asian (EAS) AF: 0.435 AC: 2240 AN: 5144

South Asian (SAS) AF: 0.421 AC: 2024 AN: 4812

European-Finnish (FIN) AF: 0.265 AC: 2798 AN: 10572

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19082 AN: 67992

Other (OTH) AF: 0.301 AC: 636 AN: 2110

Alfa AF: 0.280 Hom.: 10835

Bravo AF: 0.262

Asia WGS AF: 0.424 AC: 1474 AN: 3478

EpiCase AF: 0.300

EpiControl AF: 0.304

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	2	Autosomal dominant nonsyndromic hearing loss 12 (2)
-	-	2	Autosomal recessive nonsyndromic hearing loss 21 (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	4.3
DANN	Benign	0.81
PhyloP100		-0.55
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10502247; hg19: chr11-120998942; COSMIC: COSV50767501; COSMIC: COSV50767501;