Variant 10-112283783-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_058222.3(TECTB):c.49G>A(p.Ala17Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

TECTB
NM_058222.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.73

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]

TECTB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15354145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TECTB	NM_058222.3 linkuse as main transcript	c.49G>A	p.Ala17Thr	missense_variant	2/11	ENST00000646139.2	NP_478129.1	Q96PL2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TECTB	ENST00000646139.2 linkuse as main transcript	c.49G>A	p.Ala17Thr	missense_variant	2/11		NM_058222.3	ENSP00000494896.1	Q96PL2
TECTB	ENST00000369422.4 linkuse as main transcript	c.49G>A	p.Ala17Thr	missense_variant	1/10	1		ENSP00000358430.3	Q96PL2
TECTB	ENST00000643850.1 linkuse as main transcript	c.49G>A	p.Ala17Thr	missense_variant	2/11			ENSP00000495832.1	A0A2R8YGB5
TECTB	ENST00000645243.1 linkuse as main transcript	c.49G>A	p.Ala17Thr	missense_variant	2/11			ENSP00000495514.1	A0A2R8Y6R9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250826

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135534

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:

0.0000137

AC:

AN:

1461626

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727106

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:

0.0000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000606

Hom.:

Bravo

AF:

0.0000113

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

Ambry Genetics

Sep 27, 2021

The c.49G>A (p.A17T) alteration is located in exon 1 (coding exon 1) of the TECTB gene. This alteration results from a G to A substitution at nucleotide position 49, causing the alanine (A) at amino acid position 17 to be replaced by a threonine (T). 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

Benign

0.12

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.076

.;T;.;T

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.079

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.69

T;.;T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.90

.;L;.;L

MutationTaster

Benign

0.91

PrimateAI

Benign

0.45

PROVEAN

Benign

0.090

.;.;.;N

REVEL

Benign

0.13

Sift

Benign

0.43

.;.;.;T

Sift4G

Benign

0.14

.;.;.;T

Polyphen

0.20

.;B;.;B

Vest4

0.51

MutPred

0.30

Gain of ubiquitination at K18 (P = 0.0882);Gain of ubiquitination at K18 (P = 0.0882);Gain of ubiquitination at K18 (P = 0.0882);Gain of ubiquitination at K18 (P = 0.0882);

MVP

0.56

MPC

0.040

ClinPred

0.27

GERP RS

4.8

Varity_R

0.090

gMVP

0.53

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over