chr11-121110699-T-C

Position:

• chr11-121110699-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005422.4(TECTA):​c.486+1201T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 152,144 control chromosomes in the GnomAD database, including 42,601 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 0.75 (42601 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: TECTA NM_005422.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TECTA	NM_005422.4	c.486+1201T>C		intron_variant		ENST00000392793.6	NP_005413.2
TBCEL-TECTA	NM_001378761.1	c.1443+1201T>C		intron_variant			NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6	c.486+1201T>C		intron_variant		5	NM_005422.4	ENSP00000376543.1
TBCEL-TECTA	ENST00000645041.1	c.1395+1201T>C		intron_variant				ENSP00000496315.1

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113311 AN: 152022 Hom.: 42569 Cov.: 32

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.769

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.826

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.725

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 ASJ exome AF: 0.500

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.745 AC: 113399 AN: 152140 Hom.: 42601 Cov.: 32 AF XY: 0.744 AC XY: 55351 AN XY: 74380

Gnomad4 AFR AF: 0.683

Gnomad4 AMR AF: 0.770

Gnomad4 ASJ AF: 0.792

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.826

Gnomad4 NFE AF: 0.782

Gnomad4 OTH AF: 0.724

Alfa AF: 0.766 Hom.: 57636

Bravo AF: 0.744

Asia WGS AF: 0.613 AC: 2134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.7
DANN	Benign	0.58

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: rs1829; hg19: chr11-120981408;