rs5934665

Variant names:

• chrX-9642410-G-A
• rs5934665
• NM_005647.4:c.-43+2050G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-9642410-G-A
• chrX-9642410-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005647.4(TBL1X):​c.-43+2050G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.55 (11978 hom., 18285 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: TBL1X NM_005647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBL1X	NM_005647.4	c.-43+2050G>A		intron_variant	Intron 3 of 17	ENST00000645353.2	NP_005638.1
TBL1X	NM_001139466.1	c.-43+2050G>A		intron_variant	Intron 3 of 17		NP_001132938.1
TBL1X	NM_001139467.1	c.-51+2050G>A		intron_variant	Intron 3 of 16		NP_001132939.1
TBL1X	NM_001139468.1	c.-51+2050G>A		intron_variant	Intron 4 of 17		NP_001132940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBL1X	ENST00000645353.2	c.-43+2050G>A		intron_variant	Intron 3 of 17		NM_005647.4	ENSP00000496215.1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 60593 AN: 110716 Hom.: 11972 Cov.: 23

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.791

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.556

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.569

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: 0.547 AC: 60614 AN: 110771 Hom.: 11978 Cov.: 23 AF XY: 0.553 AC XY: 18285 AN XY: 33039

African (AFR) AF: 0.449 AC: 13687 AN: 30494

American (AMR) AF: 0.671 AC: 6987 AN: 10419

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1216 AN: 2632

East Asian (EAS) AF: 0.979 AC: 3464 AN: 3540

South Asian (SAS) AF: 0.792 AC: 2084 AN: 2630

European-Finnish (FIN) AF: 0.543 AC: 3177 AN: 5846

Middle Eastern (MID) AF: 0.556 AC: 119 AN: 214

European-Non Finnish (NFE) AF: 0.543 AC: 28688 AN: 52816

Other (OTH) AF: 0.574 AC: 869 AN: 1514

Alfa AF: 0.555 Hom.: 52576

Bravo AF: 0.555

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.30
DANN	Benign	0.43
PhyloP100		-1.2
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: rs5934665; hg19: chrX-9610450;