11-121137576-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001378761.1(TBCEL-TECTA):c.4054C>T(p.Arg1352Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000314 in 1,613,930 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1352L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0014 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

TBCEL-TECTA
NM_001378761.1 missense

Scores

Clinical Significance

Likely benign reviewed by expert panel U:3B:7

Conservation

PhyloP100: 1.51

Publications

4 publications found

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: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]

TBCEL-TECTA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015393078).

BP6

Variant 11-121137576-C-T is Benign according to our data. Variant chr11-121137576-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 178538.Status of the report is reviewed_by_expert_panel, 3 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378761.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECTA	NM_005422.4	MANE Select	c.3097C>T	p.Arg1033Trp	missense	Exon 11 of 24	NP_005413.2
	TBCEL-TECTA	NM_001378761.1		c.4054C>T	p.Arg1352Trp	missense	Exon 17 of 30	NP_001365690.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TECTA	ENST00000392793.6	TSL:5 MANE Select	c.3097C>T	p.Arg1033Trp	missense	Exon 11 of 24	ENSP00000376543.1
TECTA	ENST00000264037.2	TSL:1	c.3097C>T	p.Arg1033Trp	missense	Exon 10 of 23	ENSP00000264037.2
TECTA	ENST00000642222.1		c.3097C>T	p.Arg1033Trp	missense	Exon 11 of 24	ENSP00000493855.1

Frequencies

GnomAD3 genomes

AF:

0.00140

AC:

212

AN:

151920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00322

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000974

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000346

AC:

AN:

251328

AF XY:

0.000243

show subpopulations

Gnomad AFR exome

AF:

0.00363

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000381

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000200

AC:

293

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

128

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00349

AC:

117

AN:

33480

American (AMR)

AF:

0.000693

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.000227

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000881

AC:

AN:

1112012

Other (OTH)

AF:

0.000480

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00140

AC:

213

AN:

152038

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

109

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.00323

AC:

134

AN:

41482

American (AMR)

AF:

0.00419

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000976

AC:

AN:

5122

South Asian (SAS)

AF:

0.000208

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67974

Other (OTH)

AF:

0.00142

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000356

Hom.:

Bravo

AF:

0.00188

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000387

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:reviewed by expert panel

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

not specified (3)

Nonsyndromic genetic hearing loss (1)

TECTA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.54

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.015

MetaSVM

Uncertain

0.41

MutationAssessor

Uncertain

2.2

PhyloP100

1.5

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.55

Sift

Uncertain

0.027

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.85

MVP

0.92

MPC

1.0

ClinPred

0.037

GERP RS

4.3

Varity_R

0.29

gMVP

0.72

Mutation Taster

=5/95

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over