NM_005647.4:c.-43+6339G>A

Variant names:

• chrX-9646699-G-A
• rs2188766
• NM_005647.4:c.-43+6339G>A

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+6339G>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 0.56 (12566 hom., 18681 hem., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: TBL1X NM_005647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367
• 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=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005647.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBL1X	NM_005647.4	MANE Select	c.-43+6339G>A		intron	N/A	NP_005638.1
	TBL1X	NM_001139466.1		c.-43+6339G>A		intron	N/A	NP_001132938.1
	TBL1X	NM_001139467.1		c.-51+6339G>A		intron	N/A	NP_001132939.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBL1X	ENST00000645353.2	MANE Select	c.-43+6339G>A		intron	N/A	ENSP00000496215.1
	TBL1X	ENST00000380961.5	TSL:1	c.-51+6339G>A		intron	N/A	ENSP00000370348.1
	TBL1X	ENST00000407597.7	TSL:2	c.-43+6339G>A		intron	N/A	ENSP00000385988.2

Frequencies

GnomAD3 genomes AF: 0.561 AC: 62199 AN: 110784 Hom.: 12561 Cov.: 24

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.980

Gnomad SAS AF: 0.786

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.562

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.567

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: 0.561 AC: 62216 AN: 110837 Hom.: 12566 Cov.: 24 AF XY: 0.565 AC XY: 18681 AN XY: 33069

African (AFR) AF: 0.499 AC: 15197 AN: 30480

American (AMR) AF: 0.677 AC: 7077 AN: 10456

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1204 AN: 2634

East Asian (EAS) AF: 0.980 AC: 3447 AN: 3517

South Asian (SAS) AF: 0.787 AC: 2080 AN: 2643

European-Finnish (FIN) AF: 0.568 AC: 3331 AN: 5864

Middle Eastern (MID) AF: 0.570 AC: 122 AN: 214

European-Non Finnish (NFE) AF: 0.541 AC: 28573 AN: 52843

Other (OTH) AF: 0.572 AC: 861 AN: 1506

Alfa AF: 0.560 Hom.: 21635

Bravo AF: 0.570

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.063
DANN	Benign	0.51
PhyloP100		-0.37
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: rs2188766; hg19: chrX-9614739;