11-121139091-C-T

Variant names:

• chr11-121139091-C-T
• rs620778
• NM_005422.4:c.3543+1069C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000392793.6(TECTA):​c.3543+1069C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,134 control chromosomes in the GnomAD database, including 11,879 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (11879 hom., cov: 32)
• Consequence: TECTA ENST00000392793.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000392793.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECTA	NM_005422.4	MANE Select	c.3543+1069C>T		intron	N/A	NP_005413.2
	TBCEL-TECTA	NM_001378761.1		c.4500+1069C>T		intron	N/A	NP_001365690.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECTA	ENST00000392793.6	TSL:5 MANE Select	c.3543+1069C>T		intron	N/A	ENSP00000376543.1
	TECTA	ENST00000264037.2	TSL:1	c.3543+1069C>T		intron	N/A	ENSP00000264037.2
	TECTA	ENST00000642222.1		c.3543+1069C>T		intron	N/A	ENSP00000493855.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49699 AN: 152016 Hom.: 11863 Cov.: 32

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.00442

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.327 AC: 49754 AN: 152134 Hom.: 11879 Cov.: 32 AF XY: 0.318 AC XY: 23651 AN XY: 74380

African (AFR) AF: 0.677 AC: 28075 AN: 41488

American (AMR) AF: 0.191 AC: 2923 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 562 AN: 3466

East Asian (EAS) AF: 0.00424 AC: 22 AN: 5186

South Asian (SAS) AF: 0.146 AC: 706 AN: 4824

European-Finnish (FIN) AF: 0.215 AC: 2278 AN: 10590

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14335 AN: 67982

Other (OTH) AF: 0.302 AC: 637 AN: 2112

Alfa AF: 0.267 Hom.: 2502

Bravo AF: 0.342

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.4
DANN	Benign	0.82
PhyloP100		0.26
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: rs620778; hg19: chr11-121009800;