rs2283693

Variant names:

• chrX-9697023-G-A
• rs2283693
• NM_005647.4:c.1054-346G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005647.4(TBL1X):​c.1054-346G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 111,108 control chromosomes in the GnomAD database, including 5,779 homozygotes. There are 12,109 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 0.37 (5779 hom., 12109 hem., cov: 23)
• Consequence: TBL1X NM_005647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 1 publications found

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBL1X	NM_005647.4	c.1054-346G>A		intron_variant	Intron 11 of 17	ENST00000645353.2	NP_005638.1
TBL1X	NM_001139466.1	c.1054-346G>A		intron_variant	Intron 11 of 17		NP_001132938.1
TBL1X	NM_001139467.1	c.901-346G>A		intron_variant	Intron 10 of 16		NP_001132939.1
TBL1X	NM_001139468.1	c.901-346G>A		intron_variant	Intron 11 of 17		NP_001132940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBL1X	ENST00000645353.2	c.1054-346G>A		intron_variant	Intron 11 of 17		NM_005647.4	ENSP00000496215.1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 41363 AN: 111056 Hom.: 5779 Cov.: 23

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.399

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.373 AC: 41388 AN: 111108 Hom.: 5779 Cov.: 23 AF XY: 0.363 AC XY: 12109 AN XY: 33388

African (AFR) AF: 0.280 AC: 8572 AN: 30663

American (AMR) AF: 0.443 AC: 4618 AN: 10428

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 932 AN: 2638

East Asian (EAS) AF: 0.216 AC: 763 AN: 3528

South Asian (SAS) AF: 0.459 AC: 1210 AN: 2636

European-Finnish (FIN) AF: 0.314 AC: 1856 AN: 5902

Middle Eastern (MID) AF: 0.431 AC: 93 AN: 216

European-Non Finnish (NFE) AF: 0.424 AC: 22446 AN: 52922

Other (OTH) AF: 0.395 AC: 594 AN: 1504

Alfa AF: 0.405 Hom.: 14288

Bravo AF: 0.375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.024
DANN	Benign	0.36
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2283693; hg19: chrX-9665063;