11-121146129-C-T

Variant names:

• chr11-121146129-C-T
• rs7130952
• NM_005422.4:c.4105+13C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001378761.1(TBCEL-TECTA):​c.5062+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: TBCEL-TECTA NM_001378761.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0420
• Publications: 7 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 -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 VariationId is 45330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378761.1. 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.4105+13C>T		intron	N/A	NP_005413.2
	TBCEL-TECTA	NM_001378761.1		c.5062+13C>T		intron	N/A	NP_001365690.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECTA	ENST00000392793.6	TSL:5 MANE Select	c.4105+13C>T		intron	N/A	ENSP00000376543.1
	TECTA	ENST00000264037.2	TSL:1	c.4105+13C>T		intron	N/A	ENSP00000264037.2
	TECTA	ENST00000642222.1		c.4105+13C>T		intron	N/A	ENSP00000493855.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38333 AN: 152104 Hom.: 5903 Cov.: 33

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

GnomAD2 exomes AF: 0.180 AC: 42174 AN: 234122 AF XY: 0.179

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 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.: 32 AF XY: 0.199 AC XY: 143851 AN XY: 722082

African (AFR) AF: 0.440 AC: 14720 AN: 33450

American (AMR) AF: 0.110 AC: 4934 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 3954 AN: 26134

East Asian (EAS) AF: 0.00139 AC: 55 AN: 39692

South Asian (SAS) AF: 0.137 AC: 11772 AN: 86178

European-Finnish (FIN) AF: 0.221 AC: 9630 AN: 43562

Middle Eastern (MID) AF: 0.173 AC: 920 AN: 5314

European-Non Finnish (NFE) AF: 0.211 AC: 234970 AN: 1111404

Other (OTH) AF: 0.197 AC: 11851 AN: 60274

GnomAD4 genome AF: 0.252 AC: 38354 AN: 152222 Hom.: 5910 Cov.: 33 AF XY: 0.245 AC XY: 18254 AN XY: 74422

African (AFR) AF: 0.424 AC: 17620 AN: 41524

American (AMR) AF: 0.157 AC: 2396 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 537 AN: 3472

East Asian (EAS) AF: 0.00424 AC: 22 AN: 5188

South Asian (SAS) AF: 0.146 AC: 703 AN: 4828

European-Finnish (FIN) AF: 0.215 AC: 2274 AN: 10592

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14082 AN: 68000

Other (OTH) AF: 0.242 AC: 511 AN: 2112

Alfa AF: 0.218 Hom.: 1136

Bravo AF: 0.256

Asia WGS AF: 0.0850 AC: 295 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Autosomal dominant nonsyndromic hearing loss 12 (1)
-	-	1	Autosomal recessive nonsyndromic hearing loss 21 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.77
DANN	Benign	0.51
PhyloP100		-0.042
Mutation Taster		=100/0	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: rs7130952; hg19: chr11-121016838; COSMIC: COSV50707770;