Variant chr11-121128116-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_005422.4(TECTA):c.2139C>G(p.Cys713Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,642 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TECTA
NM_005422.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00300

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.943

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TECTA	NM_005422.4 linkuse as main transcript	c.2139C>G	p.Cys713Trp	missense_variant	9/24	ENST00000392793.6	NP_005413.2
TBCEL-TECTA	NM_001378761.1 linkuse as main transcript	c.3096C>G	p.Cys1032Trp	missense_variant	15/30		NP_001365690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TECTA	ENST00000392793.6 linkuse as main transcript	c.2139C>G	p.Cys713Trp	missense_variant	9/24	5	NM_005422.4	ENSP00000376543	P4
TECTA	ENST00000264037.2 linkuse as main transcript	c.2139C>G	p.Cys713Trp	missense_variant	8/23	1		ENSP00000264037	P4
TECTA	ENST00000642222.1 linkuse as main transcript	c.2139C>G	p.Cys713Trp	missense_variant	9/24			ENSP00000493855	A1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250066

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135244

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1460642

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726668

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.25

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.91

D;.;D

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.81

.;T;T

M_CAP

Uncertain

0.27

MetaRNN

Pathogenic

0.94

D;D;D

MetaSVM

Uncertain

0.20

MutationAssessor

Uncertain

2.6

M;.;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-8.8

D;.;D

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0010

D;.;D

Sift4G

Pathogenic

0.0

D;.;D

Polyphen

1.0

D;.;D

Vest4

0.96

MutPred

0.78

Loss of catalytic residue at L714 (P = 0.0081);Loss of catalytic residue at L714 (P = 0.0081);Loss of catalytic residue at L714 (P = 0.0081);

MVP

0.79

MPC

1.3

ClinPred

0.85

GERP RS

0.65

Varity_R

0.97

gMVP

1.0

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over