X-9683799-T-A

Variant names:

• chrX-9683799-T-A
• rs2732883
• NM_005647.4:c.212-244T>A

Variant summary

Our verdict is Benign. The variant received -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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TBL1X	NM_005647.4	c.212-244T>A		intron_variant	Intron 5 of 17	ENST00000645353.2	NP_005638.1
TBL1X	NM_001139466.1	c.212-244T>A		intron_variant	Intron 5 of 17		NP_001132938.1
TBL1X	NM_001139467.1	c.59-244T>A		intron_variant	Intron 4 of 16		NP_001132939.1
TBL1X	NM_001139468.1	c.59-244T>A		intron_variant	Intron 5 of 17		NP_001132940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBL1X	ENST00000645353.2	c.212-244T>A		intron_variant	Intron 5 of 17		NM_005647.4	ENSP00000496215.1

Frequencies

GnomAD3 genomes AF: 0.875 AC: 96117 AN: 109838 Hom.: 29787 Cov.: 22

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

African (AFR) AF: 0.902 AC: 27220 AN: 30192

American (AMR) AF: 0.930 AC: 9592 AN: 10314

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 2139 AN: 2618

East Asian (EAS) AF: 1.00 AC: 3487 AN: 3487

South Asian (SAS) AF: 0.966 AC: 2435 AN: 2520

European-Finnish (FIN) AF: 0.816 AC: 4671 AN: 5724

Middle Eastern (MID) AF: 0.815 AC: 176 AN: 216

European-Non Finnish (NFE) AF: 0.847 AC: 44609 AN: 52653

Other (OTH) AF: 0.875 AC: 1305 AN: 1491

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.73
DANN	Benign	0.39
PhyloP100		-0.25
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

Publications

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Other links and lift over

dbSNP: rs2732883; hg19: chrX-9651839;