11-121118393-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005422.4(TECTA):​c.878A>G​(p.Tyr293Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000991 in 1,614,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

TECTA
NM_005422.4 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 3.71
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.1534707).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TECTANM_005422.4 linkc.878A>G p.Tyr293Cys missense_variant Exon 7 of 24 ENST00000392793.6 NP_005413.2 O75443
TBCEL-TECTANM_001378761.1 linkc.1835A>G p.Tyr612Cys missense_variant Exon 13 of 30 NP_001365690.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TECTAENST00000392793.6 linkc.878A>G p.Tyr293Cys missense_variant Exon 7 of 24 5 NM_005422.4 ENSP00000376543.1 O75443
TECTAENST00000264037.2 linkc.878A>G p.Tyr293Cys missense_variant Exon 6 of 23 1 ENSP00000264037.2 O75443
TECTAENST00000642222.1 linkc.878A>G p.Tyr293Cys missense_variant Exon 7 of 24 ENSP00000493855.1 A0A2R8YDL0

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152206
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000278
AC:
7
AN:
251422
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000173
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000752
AC:
11
AN:
1461858
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000179
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:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152324
Hom.:
0
Cov.:
32
AF XY:
0.0000403
AC XY:
3
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000378
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 11, 2017
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The p.Tyr293Cys variant in TECTA has not been previously reported in individuals with hearing loss, but has been identified in 7/33582 of Latino chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs185351501). Although this variant has been seen in the general population, i ts frequency is not high enough to rule out a pathogenic role. Computational pr ediction tools and conservation analyses suggest that this variant may not impac t the protein, though this information is not predictive enough to rule out path ogenicity. In summary, the clinical significance of the p.Tyr293Cys variant is u ncertain. -

Inborn genetic diseases Uncertain:1
May 14, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.878A>G (p.Y293C) alteration is located in exon 6 (coding exon 6) of the TECTA gene. This alteration results from a A to G substitution at nucleotide position 878, causing the tyrosine (Y) at amino acid position 293 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided Uncertain:1
Apr 23, 2025
GeneDx
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 21520338, 31554319, 9590290) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.19
T;.;T
Eigen
Benign
-0.096
Eigen_PC
Benign
0.11
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.91
.;D;D
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.15
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
N;.;N
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-1.3
N;.;N
REVEL
Benign
0.23
Sift
Benign
0.17
T;.;T
Sift4G
Benign
0.17
T;.;T
Polyphen
0.26
B;.;B
Vest4
0.54
MVP
0.84
MPC
0.58
ClinPred
0.21
T
GERP RS
4.5
Varity_R
0.10
gMVP
0.58

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.

Other links and lift over

dbSNP: rs185351501; hg19: chr11-120989102; API