X-9687887-G-A

Variant names:

• chrX-9687887-G-A
• rs2732886
• NM_005647.4:c.358-130G>A

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.358-130G>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 0.79 (25260 hom., 24980 hem., cov: 21)
  • Exomes 𝑓: 0.89 (267899 hom. 268753 hem.)
  • Failed GnomAD Quality Control
• Consequence: TBL1X NM_005647.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.156

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=-0.87).
• BP6: Variant X-9687887-G-A is Benign according to our data. Variant chrX-9687887-G-A is described in ClinVar as [Benign]. Clinvar id is 1221121.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.358-130G>A		intron_variant	Intron 6 of 17	ENST00000645353.2	NP_005638.1
TBL1X	NM_001139466.1	c.358-130G>A		intron_variant	Intron 6 of 17		NP_001132938.1
TBL1X	NM_001139467.1	c.205-130G>A		intron_variant	Intron 5 of 16		NP_001132939.1
TBL1X	NM_001139468.1	c.205-130G>A		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.358-130G>A		intron_variant	Intron 6 of 17		NM_005647.4	ENSP00000496215.1

Frequencies

GnomAD3 genomes AF: 0.792 AC: 86164 AN: 108754 Hom.: 25261 Cov.: 21

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.889

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.953

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.833

Gnomad NFE AF: 0.892

Gnomad OTH AF: 0.802

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.894 AC: 866349 AN: 969320 Hom.: 267899 AF XY: 0.898 AC XY: 268753 AN XY: 299234

African (AFR) AF: 0.518 AC: 11189 AN: 21620

American (AMR) AF: 0.915 AC: 13567 AN: 14834

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 11640 AN: 13697

East Asian (EAS) AF: 1.00 AC: 25643 AN: 25647

South Asian (SAS) AF: 0.955 AC: 35478 AN: 37144

European-Finnish (FIN) AF: 0.879 AC: 30693 AN: 34906

Middle Eastern (MID) AF: 0.858 AC: 2415 AN: 2815

European-Non Finnish (NFE) AF: 0.900 AC: 699985 AN: 777978

Other (OTH) AF: 0.879 AC: 35739 AN: 40679

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.792 AC: 86193 AN: 108805 Hom.: 25260 Cov.: 21 AF XY: 0.800 AC XY: 24980 AN XY: 31223

African (AFR) AF: 0.526 AC: 15681 AN: 29832

American (AMR) AF: 0.889 AC: 9079 AN: 10210

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2206 AN: 2622

East Asian (EAS) AF: 1.00 AC: 3442 AN: 3442

South Asian (SAS) AF: 0.954 AC: 2319 AN: 2430

European-Finnish (FIN) AF: 0.875 AC: 4927 AN: 5632

Middle Eastern (MID) AF: 0.839 AC: 177 AN: 211

European-Non Finnish (NFE) AF: 0.892 AC: 46627 AN: 52293

Other (OTH) AF: 0.805 AC: 1180 AN: 1465

Alfa AF: 0.798 Hom.: 5341

Bravo AF: 0.781

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	-0.87
CADD	Benign	3.4
DANN	Benign	0.43
PhyloP100		-0.16
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: rs2732886; hg19: chrX-9655927;