rs145916279

Positions:

• chr11-121102653-T-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_005422.4(TECTA):​c.-1-12T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0049 in 1,610,968 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0034 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (32 hom.)
• Consequence: TECTA NM_005422.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.5342
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 2.14

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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 11-121102653-T-C is Benign according to our data. Variant chr11-121102653-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 227093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00344 (524/152316) while in subpopulation NFE AF= 0.00542 (369/68034). AF 95% confidence interval is 0.00497. There are 1 homozygotes in gnomad4. There are 224 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 32 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TECTA	NM_005422.4	c.-1-12T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000392793.6	NP_005413.2
TBCEL-TECTA	NM_001378761.1	c.957-12T>C		splice_polypyrimidine_tract_variant, intron_variant			NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TECTA	ENST00000392793.6	c.-1-12T>C		splice_polypyrimidine_tract_variant, intron_variant		5	NM_005422.4	ENSP00000376543	P4
TECTA	ENST00000642222.1	c.-1-12T>C		splice_polypyrimidine_tract_variant, intron_variant				ENSP00000493855	A1
TECTA	ENST00000264037.2			upstream_gene_variant		1		ENSP00000264037	P4

Frequencies

GnomAD3 genomes AF: 0.00344 AC: 524 AN: 152198 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000845

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00367

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00544

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00399 AC: 994 AN: 249138 Hom.: 7 AF XY: 0.00387 AC XY: 523 AN XY: 135094

Gnomad AFR exome AF: 0.000823

Gnomad AMR exome AF: 0.00481

Gnomad ASJ exome AF: 0.00270

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000753

Gnomad FIN exome AF: 0.00342

Gnomad NFE exome AF: 0.00556

Gnomad OTH exome AF: 0.0111

GnomAD4 exome AF: 0.00505 AC: 7364 AN: 1458652 Hom.: 32 Cov.: 30 AF XY: 0.00494 AC XY: 3587 AN XY: 725920

Gnomad4 AFR exome AF: 0.000629

Gnomad4 AMR exome AF: 0.00508

Gnomad4 ASJ exome AF: 0.00314

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00107

Gnomad4 FIN exome AF: 0.00355

Gnomad4 NFE exome AF: 0.00581

Gnomad4 OTH exome AF: 0.00453

GnomAD4 genome AF: 0.00344 AC: 524 AN: 152316 Hom.: 1 Cov.: 32 AF XY: 0.00301 AC XY: 224 AN XY: 74474

Gnomad4 AFR AF: 0.000842

Gnomad4 AMR AF: 0.00360

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00367

Gnomad4 NFE AF: 0.00542

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00513 Hom.: 1

Bravo AF: 0.00342

Asia WGS AF: 0.00202 AC: 7 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 30, 2012	-13T>C in Promoter of TECTA: This variant is not expected to have clinical signi ficance because it has been identified in 0.6% (40/7020) of European American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washingt -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Nonsyndromic Hearing Loss, Dominant Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 25, 2020

- -

Hearing loss, autosomal recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.53
dbscSNV1_RF	Benign	0.40
SpliceAI score (max)		0.13		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: rs145916279; hg19: chr11-120973362;