chr11-121102653-T-C

Position:

chr11-121102653-T-C

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

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

Variant links:

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]

TECTA links:

TBCEL-TECTA (HGNC:):

TBCEL-TECTA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.-1-12T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000392793.6	NP_005413.2
TBCEL-TECTA	NM_001378761.1 linkuse as main transcript	c.957-12T>C		splice_polypyrimidine_tract_variant, intron_variant			NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
TECTA	ENST00000392793.6 linkuse as main transcript	c.-1-12T>C	splice_polypyrimidine_tract_variant, intron_variant	5	NM_005422.4	ENSP00000376543	P4
TECTA	ENST00000642222.1 linkuse as main transcript	c.-1-12T>C	splice_polypyrimidine_tract_variant, intron_variant			ENSP00000493855	A1
TECTA	ENST00000264037.2 linkuse as main transcript		upstream_gene_variant	1		ENSP00000264037	P4

Frequencies

GnomAD3 genomes

AF:

0.00344

AC:

524

AN:

152198

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00387

AC XY:

523

AN XY:

135094

show subpopulations

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.:

Cov.:

AF XY:

0.00494

AC XY:

3587

AN XY:

725920

show subpopulations

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.:

Cov.:

AF XY:

0.00301

AC XY:

224

AN XY:

74474

show subpopulations

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.:

Bravo

AF:

0.00342

Asia WGS

AF:

0.00202

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over