rs2188766

chrX-9646699-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_005647.4(TBL1X):c.-43+6339G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.56 (12566 hom., 18681 hem., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: TBL1X NM_005647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS2: High Homozygotes in GnomAd at 12561 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBL1X	NM_005647.4	c.-43+6339G>A		intron_variant		ENST00000645353.2
TBL1X	NM_001139466.1	c.-43+6339G>A		intron_variant
TBL1X	NM_001139467.1	c.-51+6339G>A		intron_variant
TBL1X	NM_001139468.1	c.-51+6339G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBL1X	ENST00000645353.2	c.-43+6339G>A		intron_variant			NM_005647.4

Frequencies

GnomAD3 genomes AF: 0.561 AC: 62199 AN: 110784 Hom.: 12561 Cov.: 24 AF XY: 0.565 AC XY: 18661 AN XY: 33006

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.980

Gnomad SAS AF: 0.786

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.562

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.567

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

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.561 AC: 62216 AN: 110837 Hom.: 12566 Cov.: 24 AF XY: 0.565 AC XY: 18681 AN XY: 33069

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.980

Gnomad4 SAS AF: 0.787

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.572

Alfa AF: 0.560 Hom.: 14635

Bravo AF: 0.570

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.063
Dann	Benign	0.51

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: rs2188766; hg19: chrX-9614739;