11-121102807-C-T

Position:

• chr11-121102807-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005422.4(TECTA):​c.64+78C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 1,230,138 control chromosomes in the GnomAD database, including 525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (269 hom., cov: 32)
  • Exomes 𝑓: 0.012 (256 hom.)
• Consequence: TECTA NM_005422.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.06

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:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 11-121102807-C-T is Benign according to our data. Variant chr11-121102807-C-T is described in ClinVar as [Benign]. Clinvar id is 1283274.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TECTA	NM_005422.4	c.64+78C>T		intron_variant		ENST00000392793.6
TBCEL-TECTA	NM_001378761.1	c.1021+78C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TECTA	ENST00000392793.6	c.64+78C>T		intron_variant		5	NM_005422.4	P4
TECTA	ENST00000264037.2	c.64+78C>T		intron_variant		1		P4
TECTA	ENST00000642222.1	c.64+78C>T		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.0375 AC: 5698 AN: 152070 Hom.: 268 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0178

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0313

Gnomad FIN AF: 0.000566

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.00889

Gnomad OTH AF: 0.0311

GnomAD4 exome AF: 0.0121 AC: 13072 AN: 1077950 Hom.: 256 AF XY: 0.0130 AC XY: 7192 AN XY: 553496

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.0108

Gnomad4 ASJ exome AF: 0.0171

Gnomad4 EAS exome AF: 0.000105

Gnomad4 SAS exome AF: 0.0291

Gnomad4 FIN exome AF: 0.000602

Gnomad4 NFE exome AF: 0.00796

Gnomad4 OTH exome AF: 0.0174

GnomAD4 genome AF: 0.0376 AC: 5716 AN: 152188 Hom.: 269 Cov.: 32 AF XY: 0.0364 AC XY: 2712 AN XY: 74408

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.0178

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0321

Gnomad4 FIN AF: 0.000566

Gnomad4 NFE AF: 0.00890

Gnomad4 OTH AF: 0.0307

Alfa AF: 0.0257 Hom.: 21

Bravo AF: 0.0427

Asia WGS AF: 0.0150 AC: 54 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	15
DANN	Benign	0.57

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: rs56358414; hg19: chr11-120973516;