rs876658015

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005422.4(TECTA):​c.187C>A​(p.Arg63Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

TECTA
NM_005422.4 missense

Scores

2
10
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.63
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TECTANM_005422.4 linkc.187C>A p.Arg63Ser missense_variant Exon 3 of 24 ENST00000392793.6 NP_005413.2 O75443
TBCEL-TECTANM_001378761.1 linkc.1144C>A p.Arg382Ser missense_variant Exon 9 of 30 NP_001365690.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TECTAENST00000392793.6 linkc.187C>A p.Arg63Ser missense_variant Exon 3 of 24 5 NM_005422.4 ENSP00000376543.1 O75443
TBCEL-TECTAENST00000645041.1 linkc.1096C>A p.Arg366Ser missense_variant Exon 8 of 10 ENSP00000496315.1 A0A2R8YFB7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.47
BayesDel_addAF
Pathogenic
0.29
D
BayesDel_noAF
Pathogenic
0.18
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
.;T;.;T
Eigen
Uncertain
0.40
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.87
D;.;T;T
M_CAP
Benign
0.025
T
MetaRNN
Uncertain
0.58
D;D;D;D
MetaSVM
Benign
-0.43
T
MutationAssessor
Benign
0.87
.;L;.;L
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-0.85
.;N;.;N
REVEL
Uncertain
0.46
Sift
Benign
0.099
.;T;.;T
Sift4G
Uncertain
0.031
.;D;.;D
Polyphen
0.99
.;D;.;D
Vest4
0.74, 0.71
MutPred
0.56
.;Loss of methylation at R63 (P = 0.0687);Loss of methylation at R63 (P = 0.0687);Loss of methylation at R63 (P = 0.0687);
MVP
0.90
MPC
0.97
ClinPred
0.91
D
GERP RS
4.8
Varity_R
0.23
gMVP
0.72

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: rs876658015; hg19: chr11-120976662; API