rs3752627

Variant names:

• chrX-9603353-A-G
• rs3752627
• NM_005647.4:c.-130-36920A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005647.4(TBL1X):​c.-130-36920A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 111,337 control chromosomes in the GnomAD database, including 10,020 homozygotes. There are 15,748 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.47 (10020 hom., 15748 hem., cov: 23)
• Consequence: TBL1X NM_005647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 0 publications found

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]

TBL1X Gene-Disease associations (from GenCC):

• hypothyroidism, congenital, nongoitrous, 8

  Inheritance: XL, Unknown Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBL1X	NM_005647.4	c.-130-36920A>G		intron_variant	Intron 2 of 17	ENST00000645353.2	NP_005638.1
TBL1X	NM_001139466.1	c.-130-36920A>G		intron_variant	Intron 2 of 17		NP_001132938.1
TBL1X	NM_001139467.1	c.-138-36920A>G		intron_variant	Intron 2 of 16		NP_001132939.1
TBL1X	NM_001139468.1	c.-138-36920A>G		intron_variant	Intron 3 of 17		NP_001132940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBL1X	ENST00000645353.2	c.-130-36920A>G		intron_variant	Intron 2 of 17		NM_005647.4	ENSP00000496215.1

Frequencies

GnomAD3 genomes AF: 0.475 AC: 52807 AN: 111285 Hom.: 10024 Cov.: 23

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.476

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.475 AC: 52833 AN: 111337 Hom.: 10020 Cov.: 23 AF XY: 0.469 AC XY: 15748 AN XY: 33555

African (AFR) AF: 0.731 AC: 22383 AN: 30599

American (AMR) AF: 0.448 AC: 4722 AN: 10539

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 879 AN: 2632

East Asian (EAS) AF: 0.667 AC: 2351 AN: 3526

South Asian (SAS) AF: 0.491 AC: 1313 AN: 2676

European-Finnish (FIN) AF: 0.359 AC: 2134 AN: 5944

Middle Eastern (MID) AF: 0.537 AC: 116 AN: 216

European-Non Finnish (NFE) AF: 0.338 AC: 17890 AN: 53002

Other (OTH) AF: 0.472 AC: 722 AN: 1529

Alfa AF: 0.443 Hom.: 4171

Bravo AF: 0.498

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.17
DANN	Benign	0.31
PhyloP100		-1.5
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

Other links and lift over

dbSNP: rs3752627; hg19: chrX-9571393;