rs17321050

Positions:

• chrX-9645059-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005647.4(TBL1X):​c.-43+4699T>G variant causes a intron 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 NM_005647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.85

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBL1X	NM_005647.4	c.-43+4699T>G		intron_variant		ENST00000645353.2	NP_005638.1
TBL1X	NM_001139466.1	c.-43+4699T>G		intron_variant			NP_001132938.1
TBL1X	NM_001139467.1	c.-51+4699T>G		intron_variant			NP_001132939.1
TBL1X	NM_001139468.1	c.-51+4699T>G		intron_variant			NP_001132940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBL1X	ENST00000645353.2	c.-43+4699T>G		intron_variant			NM_005647.4	ENSP00000496215

Frequencies

GnomAD3 genomes AF: 0.292 AC: 32478 AN: 111091 Hom.: 3769 Cov.: 23 AF XY: 0.282 AC XY: 9397 AN XY: 33309

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: 16 AN: 37 Hom.: 1 Cov.: 0 AF XY: 0.478 AC XY: 11 AN XY: 23

Gnomad4 AFR exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.424

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.292 AC: 32484 AN: 111144 Hom.: 3770 Cov.: 23 AF XY: 0.282 AC XY: 9411 AN XY: 33374

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.0154

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.343

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.282

Alfa AF: 0.341 Hom.: 30997

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
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs17321050; hg19: chrX-9613099;