X-9687883-C-T

Variant names:

• chrX-9687883-C-T
• rs2521583
• NM_005647.4:c.358-134C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

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

Our verdict: Likely_benign. The variant received -6 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBL1X	NM_005647.4	c.358-134C>T		intron_variant	Intron 6 of 17	ENST00000645353.2	NP_005638.1
TBL1X	NM_001139466.1	c.358-134C>T		intron_variant	Intron 6 of 17		NP_001132938.1
TBL1X	NM_001139467.1	c.205-134C>T		intron_variant	Intron 5 of 16		NP_001132939.1
TBL1X	NM_001139468.1	c.205-134C>T		intron_variant	Intron 6 of 17		NP_001132940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBL1X	ENST00000645353.2	c.358-134C>T		intron_variant	Intron 6 of 17		NM_005647.4	ENSP00000496215.1

Frequencies

GnomAD3 genomes AF: 0.792 AC: 86216 AN: 108910 Hom.: 25216 Cov.: 21

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

African (AFR) AF: 0.516 AC: 11109 AN: 21532

American (AMR) AF: 0.915 AC: 13334 AN: 14578

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 11626 AN: 13678

East Asian (EAS) AF: 1.00 AC: 25579 AN: 25583

South Asian (SAS) AF: 0.955 AC: 35374 AN: 37054

European-Finnish (FIN) AF: 0.879 AC: 30568 AN: 34768

Middle Eastern (MID) AF: 0.859 AC: 2373 AN: 2762

European-Non Finnish (NFE) AF: 0.900 AC: 698223 AN: 775789

Other (OTH) AF: 0.879 AC: 35641 AN: 40570

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

African (AFR) AF: 0.524 AC: 15649 AN: 29883

American (AMR) AF: 0.889 AC: 9084 AN: 10221

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 2215 AN: 2631

East Asian (EAS) AF: 1.00 AC: 3439 AN: 3439

South Asian (SAS) AF: 0.954 AC: 2338 AN: 2450

European-Finnish (FIN) AF: 0.875 AC: 4938 AN: 5642

Middle Eastern (MID) AF: 0.831 AC: 177 AN: 213

European-Non Finnish (NFE) AF: 0.892 AC: 46680 AN: 52357

Other (OTH) AF: 0.802 AC: 1169 AN: 1458

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

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	-0.89
CADD	Benign	0.48
DANN	Benign	0.60
PhyloP100		-0.85
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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

dbSNP: rs2521583; hg19: chrX-9655923;