Variant X-9688032-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005647.4(TBL1X):c.373G>A(p.Asp125Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000332 in 1,205,346 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.0000027 ( 0 hom. 1 hem. )

Consequence

TBL1X
NM_005647.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 8.82

Variant links:

Genes affected

TBL1X (HGNC:11585): (transducin beta like 1 X-linked) The protein encoded by this gene has sequence similarity with members of the WD40 repeat-containing protein family. The WD40 group is a large family of proteins, which appear to have a regulatory function. It is believed that the WD40 repeats mediate protein-protein interactions and members of the family are involved in signal transduction, RNA processing, gene regulation, vesicular trafficking, cytoskeletal assembly and may play a role in the control of cytotypic differentiation. This encoded protein is found as a subunit in corepressor SMRT (silencing mediator for retinoid and thyroid receptors) complex along with histone deacetylase 3 protein. This gene is located adjacent to the ocular albinism gene and it is thought to be involved in the pathogenesis of the ocular albinism with late-onset sensorineural deafness phenotype. Four transcript variants encoding two different isoforms have been found for this gene. This gene is highly similar to the Y chromosome TBL1Y gene. [provided by RefSeq, Nov 2008]

TBL1X links:

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/exons	MANE
TBL1X	NM_005647.4 linkuse as main transcript	c.373G>A	p.Asp125Asn	missense_variant	7/18	ENST00000645353.2
TBL1X	NM_001139466.1 linkuse as main transcript	c.373G>A	p.Asp125Asn	missense_variant	7/18
TBL1X	NM_001139467.1 linkuse as main transcript	c.220G>A	p.Asp74Asn	missense_variant	6/17
TBL1X	NM_001139468.1 linkuse as main transcript	c.220G>A	p.Asp74Asn	missense_variant	7/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBL1X	ENST00000645353.2 linkuse as main transcript	c.373G>A	p.Asp125Asn	missense_variant	7/18		NM_005647.4		O60907-1

Frequencies

GnomAD3 genomes

AF:

0.00000892

AC:

AN:

112050

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34214

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1093296

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

359642

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:

0.00000357

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000892

AC:

AN:

112050

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34214

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000453

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, no assertion criteria provided

research

Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo

Feb 08, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

Cadd

Pathogenic

Dann

Uncertain

1.0

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.86

D;D;.;D;.;.;.;.;D;D

M_CAP

Benign

0.043

MetaRNN

Uncertain

0.47

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.89

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-2.0

N;N;N;D;N;.;.;.;.;.

REVEL

Benign

0.20

Sift

Benign

0.081

T;T;T;D;T;.;.;.;.;.

Sift4G

Benign

0.21

T;T;T;D;T;.;.;.;.;.

Polyphen

0.76

.;P;.;.;P;P;P;P;.;.

Vest4

0.81

MutPred

0.47

.;Loss of loop (P = 0.0374);.;.;Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);.;.;

MVP

0.81

MPC

1.0

ClinPred

0.90

GERP RS

4.9

Varity_R

0.47

gMVP

0.93

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