11-121102565-C-T

Position:

• chr11-121102565-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005422.4(TECTA):​c.-1-100C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 880,136 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0077 (6 hom., cov: 32)
  • Exomes 𝑓: 0.012 (129 hom.)
• Consequence: TECTA NM_005422.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.181

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=-0.5).
• BP6: Variant 11-121102565-C-T is Benign according to our data. Variant chr11-121102565-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1209193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00774 (1179/152272) while in subpopulation SAS AF= 0.033 (159/4824). AF 95% confidence interval is 0.0288. There are 6 homozygotes in gnomad4. There are 586 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TECTA	NM_005422.4	c.-1-100C>T		intron_variant		ENST00000392793.6	NP_005413.2
TBCEL-TECTA	NM_001378761.1	c.957-100C>T		intron_variant			NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6	c.-1-100C>T		intron_variant		5	NM_005422.4	ENSP00000376543	P4
TECTA	ENST00000642222.1	c.-1-100C>T		intron_variant				ENSP00000493855	A1

Frequencies

GnomAD3 genomes AF: 0.00778 AC: 1184 AN: 152154 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00174

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00576

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0333

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.0124

GnomAD4 exome AF: 0.0122 AC: 8862 AN: 727864 Hom.: 129 AF XY: 0.0136 AC XY: 5306 AN XY: 388812

Gnomad4 AFR exome AF: 0.00126

Gnomad4 AMR exome AF: 0.00506

Gnomad4 ASJ exome AF: 0.0181

Gnomad4 EAS exome AF: 0.0000279

Gnomad4 SAS exome AF: 0.0343

Gnomad4 FIN exome AF: 0.00457

Gnomad4 NFE exome AF: 0.0113

Gnomad4 OTH exome AF: 0.0120

GnomAD4 genome AF: 0.00774 AC: 1179 AN: 152272 Hom.: 6 Cov.: 32 AF XY: 0.00787 AC XY: 586 AN XY: 74454

Gnomad4 AFR AF: 0.00173

Gnomad4 AMR AF: 0.00562

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0330

Gnomad4 FIN AF: 0.00330

Gnomad4 NFE AF: 0.0107

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.00938 Hom.: 1

Bravo AF: 0.00711

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 25, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.4
DANN	Benign	0.67

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: rs79614045; hg19: chr11-120973274;