chr10-112286390-C-T

Variant summary

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

The NM_058222.3(TECTB):​c.482C>T​(p.Thr161Ile) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

TECTB
NM_058222.3 missense, splice_region

Scores

2
14
3
Splicing: ADA: 0.9920
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.84
Variant links:
Genes affected
TECTB (HGNC:11721): (tectorin beta) This gene encodes a non-collagenous glycoprotein component of the tectorial membrane, which covers the auditory hair cells in the cochlea of the inner ear. A similar protein in mouse functions in low-frequency hearing. [provided by RefSeq, Jul 2013]

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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
TECTBNM_058222.3 linkc.482C>T p.Thr161Ile missense_variant, splice_region_variant Exon 5 of 11 ENST00000646139.2 NP_478129.1 Q96PL2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TECTBENST00000646139.2 linkc.482C>T p.Thr161Ile missense_variant, splice_region_variant Exon 5 of 11 NM_058222.3 ENSP00000494896.1 Q96PL2
TECTBENST00000369422.4 linkc.482C>T p.Thr161Ile missense_variant, splice_region_variant Exon 4 of 10 1 ENSP00000358430.3 Q96PL2
TECTBENST00000643850.1 linkc.512C>T p.Thr171Ile missense_variant, splice_region_variant Exon 5 of 11 ENSP00000495832.1 A0A2R8YGB5
TECTBENST00000645243.1 linkc.482C>T p.Thr161Ile missense_variant, splice_region_variant Exon 5 of 11 ENSP00000495514.1 A0A2R8Y6R9

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
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
Nov 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.482C>T (p.T161I) alteration is located in exon 4 (coding exon 4) of the TECTB gene. This alteration results from a C to T substitution at nucleotide position 482, causing the threonine (T) at amino acid position 161 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.41
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.060
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.62
.;D;.;D
Eigen
Uncertain
0.68
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.87
D;.;D;D
M_CAP
Benign
0.033
D
MetaRNN
Uncertain
0.56
D;D;D;D
MetaSVM
Uncertain
0.098
D
MutationAssessor
Benign
1.1
.;L;.;L
PrimateAI
Uncertain
0.66
T
PROVEAN
Uncertain
-2.4
.;.;.;N
REVEL
Uncertain
0.43
Sift
Uncertain
0.021
.;.;.;D
Sift4G
Uncertain
0.0070
.;.;.;D
Polyphen
0.92
.;P;.;P
Vest4
0.50
MutPred
0.49
.;Loss of phosphorylation at T161 (P = 0.1821);Loss of phosphorylation at T161 (P = 0.1821);Loss of phosphorylation at T161 (P = 0.1821);
MVP
0.87
MPC
0.27
ClinPred
0.94
D
GERP RS
6.2
Varity_R
0.30
gMVP
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
0.99
dbscSNV1_RF
Pathogenic
0.89
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-114046148; API