11-121128116-C-G

Variant summary

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

The NM_005422.4(TECTA):ā€‹c.2139C>Gā€‹(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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C713R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000048 ( 0 hom. )

Consequence

TECTA
NM_005422.4 missense

Scores

8
6
5

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]

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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 UniProt
TECTANM_005422.4 linkuse as main transcriptc.2139C>G p.Cys713Trp missense_variant 9/24 ENST00000392793.6
TBCEL-TECTANM_001378761.1 linkuse as main transcriptc.3096C>G p.Cys1032Trp missense_variant 15/30

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TECTAENST00000392793.6 linkuse as main transcriptc.2139C>G p.Cys713Trp missense_variant 9/245 NM_005422.4 P4
TECTAENST00000264037.2 linkuse as main transcriptc.2139C>G p.Cys713Trp missense_variant 8/231 P4
TECTAENST00000642222.1 linkuse as main transcriptc.2139C>G p.Cys713Trp missense_variant 9/24 A1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000400
AC:
1
AN:
250066
Hom.:
0
AF XY:
0.00000739
AC XY:
1
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:
7
AN:
1460642
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
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.:
32
ExAC
AF:
0.00000824
AC:
1
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
D
BayesDel_noAF
Pathogenic
0.25
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.91
D;.;D
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.37
FATHMM_MKL
Benign
0.46
N
LIST_S2
Benign
0.81
.;T;T
M_CAP
Uncertain
0.27
D
MetaRNN
Pathogenic
0.94
D;D;D
MetaSVM
Uncertain
0.20
D
MutationAssessor
Uncertain
2.6
M;.;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.72
T
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
D
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.

Other links and lift over

dbSNP: rs768295360; hg19: chr11-120998825; API