X-9687883-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_005647.4(TBL1X):c.358-134C>T 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 0.79 (25215 hom., 25101 hem., cov: 21)
  • Exomes 𝑓: 0.89 (267121 hom. 267900 hem.)
  • Failed GnomAD Quality Control
• Consequence: TBL1X NM_005647.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.851

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant X-9687883-C-T is Benign according to our data. Variant chrX-9687883-C-T is described in ClinVar as [Benign]. Clinvar id is 1251514.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 25216 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBL1X	NM_005647.4	c.358-134C>T		intron_variant		ENST00000645353.2
TBL1X	NM_001139466.1	c.358-134C>T		intron_variant
TBL1X	NM_001139467.1	c.205-134C>T		intron_variant
TBL1X	NM_001139468.1	c.205-134C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBL1X	ENST00000645353.2	c.358-134C>T		intron_variant			NM_005647.4

Frequencies

GnomAD3 genomes AF: 0.792 AC: 86216 AN: 108910 Hom.: 25216 Cov.: 21 AF XY: 0.801 AC XY: 25066 AN XY: 31306

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.892

Gnomad OTH AF: 0.798

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.894 AC: 863827 AN: 966314 Hom.: 267121 AF XY: 0.899 AC XY: 267900 AN XY: 297994

Gnomad4 AFR exome AF: 0.516

Gnomad4 AMR exome AF: 0.915

Gnomad4 ASJ exome AF: 0.850

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.955

Gnomad4 FIN exome AF: 0.879

Gnomad4 NFE exome AF: 0.900

Gnomad4 OTH exome AF: 0.879

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.792 AC: 86246 AN: 108962 Hom.: 25215 Cov.: 21 AF XY: 0.800 AC XY: 25101 AN XY: 31368

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.889

Gnomad4 ASJ AF: 0.842

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.954

Gnomad4 FIN AF: 0.875

Gnomad4 NFE AF: 0.892

Gnomad4 OTH AF: 0.802

Alfa AF: 0.721 Hom.: 2792

Bravo AF: 0.780

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.89
Cadd	Benign	0.48
Dann	Benign	0.60

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: rs2521583; hg19: chrX-9655923;