10-112293787-C-T

Variant summary

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

The NM_058222.3(TECTB):​c.533C>T​(p.Ser178Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000743 in 1,613,988 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S178S) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

TECTB
NM_058222.3 missense

Scores

3
11
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.16
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]

Genome browser will be placed here

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.533C>T p.Ser178Phe missense_variant Exon 6 of 11 ENST00000646139.2 NP_478129.1 Q96PL2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TECTBENST00000646139.2 linkc.533C>T p.Ser178Phe missense_variant Exon 6 of 11 NM_058222.3 ENSP00000494896.1 Q96PL2
TECTBENST00000369422.4 linkc.533C>T p.Ser178Phe missense_variant Exon 5 of 10 1 ENSP00000358430.3 Q96PL2
TECTBENST00000643850.1 linkc.563C>T p.Ser188Phe missense_variant Exon 6 of 11 ENSP00000495832.1 A0A2R8YGB5
TECTBENST00000645243.1 linkc.533C>T p.Ser178Phe missense_variant Exon 6 of 11 ENSP00000495514.1 A0A2R8Y6R9

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152108
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
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:
0.0000239
AC:
6
AN:
251464
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135904
show subpopulations
Gnomad AFR exome
AF:
0.000308
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:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461880
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152108
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.0000966
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000122
Hom.:
0
Bravo
AF:
0.0000340
ESP6500AA
AF:
0.000908
AC:
4
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000494
AC:
6

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Sep 15, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.533C>T (p.S178F) alteration is located in exon 5 (coding exon 5) of the TECTB gene. This alteration results from a C to T substitution at nucleotide position 533, causing the serine (S) at amino acid position 178 to be replaced by a phenylalanine (F). 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
Pathogenic
0.61
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Pathogenic
0.24
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.36
.;T;.;T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.80
T;.;T;T
M_CAP
Uncertain
0.11
D
MetaRNN
Uncertain
0.60
D;D;D;D
MetaSVM
Uncertain
0.080
D
MutationAssessor
Uncertain
2.1
.;M;.;M
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-1.4
.;.;.;N
REVEL
Uncertain
0.63
Sift
Benign
0.10
.;.;.;T
Sift4G
Uncertain
0.0020
.;.;.;D
Polyphen
0.96
.;P;.;P
Vest4
0.79
MVP
0.74
MPC
0.14
ClinPred
0.82
D
GERP RS
5.1
Varity_R
0.19
gMVP
0.62

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: rs148150999; hg19: chr10-114053545; API