11-121129648-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_005422.4(TECTA):c.2378A>G(p.Gln793Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
TECTA
NM_005422.4 missense
NM_005422.4 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 4.56
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 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27050602).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TECTA | NM_005422.4 | c.2378A>G | p.Gln793Arg | missense_variant | 10/24 | ENST00000392793.6 | |
TBCEL-TECTA | NM_001378761.1 | c.3335A>G | p.Gln1112Arg | missense_variant | 16/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TECTA | ENST00000392793.6 | c.2378A>G | p.Gln793Arg | missense_variant | 10/24 | 5 | NM_005422.4 | P4 | |
TECTA | ENST00000264037.2 | c.2378A>G | p.Gln793Arg | missense_variant | 9/23 | 1 | P4 | ||
TECTA | ENST00000642222.1 | c.2378A>G | p.Gln793Arg | missense_variant | 10/24 | A1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 13, 2014 | The Gln793Arg variant in TECTA has not been previously reported in individuals w ith hearing loss or in large population studies. The glutamine (Gln) at position 793 is not conserved in evolutionarily distant species and one mammal (naked mo le rat) carries an arginine (Arg) at this position, raising the possibility that this change may be tolerated. Additional computational prediction tools suggest that this variant may not impact the protein, though this information is not pr edictive enough to rule out pathogenicity. In summary, while the clinical signif icance of the Gln793Arg variant is uncertain, the conservation data suggest that it is more likely to be benign. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;.;N
REVEL
Benign
Sift
Benign
T;.;T
Sift4G
Benign
T;.;T
Polyphen
P;.;P
Vest4
MutPred
Gain of methylation at Q793 (P = 0.0732);Gain of methylation at Q793 (P = 0.0732);Gain of methylation at Q793 (P = 0.0732);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at