rs877538

Positions:

• chr11-121143750-C-A

Variant summary

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

The NM_005422.4(TECTA):​c.3544-1805C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,070 control chromosomes in the GnomAD database, including 7,092 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 0.27 (7092 hom., cov: 32)
• Consequence: TECTA NM_005422.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TECTA	NM_005422.4	c.3544-1805C>A		intron_variant		ENST00000392793.6	NP_005413.2
TBCEL-TECTA	NM_001378761.1	c.4501-1805C>A		intron_variant			NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6	c.3544-1805C>A		intron_variant		5	NM_005422.4	ENSP00000376543.1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41287 AN: 151952 Hom.: 7080 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.00442

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.272 AC: 41332 AN: 152070 Hom.: 7092 Cov.: 32 AF XY: 0.265 AC XY: 19677 AN XY: 74332

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.00424

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.261

Alfa AF: 0.247 Hom.: 679

Bravo AF: 0.278

Asia WGS AF: 0.0920 AC: 320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.26

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: rs877538; hg19: chr11-121014459;