X-9683799-T-A

Position:

• chrX-9683799-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_005647.4(TBL1X):​c.212-244T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (29794 hom., 28211 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: TBL1X NM_005647.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.252

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=-0.98).
• BP6: Variant X-9683799-T-A is Benign according to our data. Variant chrX-9683799-T-A is described in ClinVar as [Benign]. Clinvar id is 1239233.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBL1X	NM_005647.4	c.212-244T>A		intron_variant		ENST00000645353.2
TBL1X	NM_001139466.1	c.212-244T>A		intron_variant
TBL1X	NM_001139467.1	c.59-244T>A		intron_variant
TBL1X	NM_001139468.1	c.59-244T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBL1X	ENST00000645353.2	c.212-244T>A		intron_variant			NM_005647.4

Frequencies

GnomAD3 genomes AF: 0.875 AC: 96117 AN: 109838 Hom.: 29787 Cov.: 22 AF XY: 0.878 AC XY: 28150 AN XY: 32056

Gnomad AFR AF: 0.901

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.930

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.966

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.806

Gnomad NFE AF: 0.847

Gnomad OTH AF: 0.873

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: 0.875 AC: 96180 AN: 109890 Hom.: 29794 Cov.: 22 AF XY: 0.878 AC XY: 28211 AN XY: 32118

Gnomad4 AFR AF: 0.902

Gnomad4 AMR AF: 0.930

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.966

Gnomad4 FIN AF: 0.816

Gnomad4 NFE AF: 0.847

Gnomad4 OTH AF: 0.875

Alfa AF: 0.740 Hom.: 2600

Bravo AF: 0.883

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.73
DANN	Benign	0.39

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: rs2732883; hg19: chrX-9651839;