dbSNP rs17321050: TBL1X:n.587T>G (chrX-9645059-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000497555.1(TBL1X):n.587T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 111,181 control chromosomes in the GnomAD database, including 3,771 homozygotes. There are 9,422 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 3770 hom., 9411 hem., cov: 23)

Exomes 𝑓: 0.43 ( 1 hom. 11 hem. )

Consequence

TBL1X
ENST00000497555.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.85

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

hypothyroidism, congenital, nongoitrous, 8
Inheritance: XL, Unknown Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

TBL1X links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TBL1X	NM_005647.4 link	c.-43+4699T>G	intron_variant	Intron 3 of 17	ENST00000645353.2	NP_005638.1	O60907-1A0A024RBV9
TBL1X	NM_001139466.1 link	c.-43+4699T>G	intron_variant	Intron 3 of 17		NP_001132938.1	O60907-1A0A024RBV9
TBL1X	NM_001139467.1 link	c.-51+4699T>G	intron_variant	Intron 3 of 16		NP_001132939.1	O60907-2
TBL1X	NM_001139468.1 link	c.-51+4699T>G	intron_variant	Intron 4 of 17		NP_001132940.1	O60907-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBL1X	ENST00000645353.2 link	c.-43+4699T>G		intron_variant	Intron 3 of 17		NM_005647.4	ENSP00000496215.1		O60907-1

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

32478

AN:

111091

Hom.:

3769

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.484

Gnomad AMR

AF:

0.242

Gnomad ASJ

AF:

0.425

Gnomad EAS

AF:

0.0157

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.343

Gnomad MID

AF:

0.270

Gnomad NFE

AF:

0.361

Gnomad OTH

AF:

0.284

GnomAD4 exome

AF:

0.432

AC:

AN:

Hom.:

Cov.:

AF XY:

0.478

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.424

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.658

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.292

AC:

32484

AN:

111144

Hom.:

3770

Cov.:

AF XY:

0.282

AC XY:

9411

AN XY:

33374

show subpopulations

African (AFR)

AF:

0.211

AC:

6461

AN:

30591

American (AMR)

AF:

0.242

AC:

2542

AN:

10519

Ashkenazi Jewish (ASJ)

AF:

0.425

AC:

1118

AN:

2630

East Asian (EAS)

AF:

0.0154

AC:

AN:

3567

South Asian (SAS)

AF:

0.156

AC:

420

AN:

2689

European-Finnish (FIN)

AF:

0.343

AC:

2025

AN:

5898

Middle Eastern (MID)

AF:

0.264

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.361

AC:

19061

AN:

52868

Other (OTH)

AF:

0.282

AC:

422

AN:

1499

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

823

1646

2470

3293

4116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.331

Hom.:

39406

Bravo

AF:

0.282

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.23

(source)

DANN

Benign

0.64

PhyloP100

-2.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs17321050

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over