NM_005647.4:c.-43+4699T>G

Variant names:

• chrX-9645059-T-G
• rs17321050
• NM_005647.4:c.-43+4699T>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.-43+4699T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 111,181 control chromosomes in the GnomAD database, including 3,771 homozygotes. There are 9,422 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 0.29 (3770 hom., 9411 hem., cov: 23)
  • Exomes 𝑓: 0.43 (1 hom. 11 hem.)
• Consequence: TBL1X NM_005647.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.85
• Publications: 2 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: Unknown, XL Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBL1X	NM_005647.4	MANE Select	c.-43+4699T>G		intron	N/A	NP_005638.1	O60907-1
	TBL1X	NM_001139466.1		c.-43+4699T>G		intron	N/A	NP_001132938.1	O60907-1
	TBL1X	NM_001139467.1		c.-51+4699T>G		intron	N/A	NP_001132939.1	O60907-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBL1X	ENST00000645353.2	MANE Select	c.-43+4699T>G		intron	N/A	ENSP00000496215.1	O60907-1
	TBL1X	ENST00000380961.5	TSL:1	c.-51+4699T>G		intron	N/A	ENSP00000370348.1	O60907-2
	TBL1X	ENST00000497555.1	TSL:1	n.587T>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.292 AC: 32478 AN: 111091 Hom.: 3769 Cov.: 23

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.0157

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.270

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.284

GnomAD4 exome AF: 0.432 AC: 16 AN: 37 Hom.: 1 Cov.: 0 AF XY: 0.478 AC XY: 11 AN XY: 23

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 1

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.424 AC: 14 AN: 33

Other (OTH) AF: 1.00 AC: 1 AN: 1

GnomAD4 genome AF: 0.292 AC: 32484 AN: 111144 Hom.: 3770 Cov.: 23 AF XY: 0.282 AC XY: 9411 AN XY: 33374

African (AFR) AF: 0.211 AC: 6461 AN: 30591

American (AMR) AF: 0.242 AC: 2542 AN: 10519

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1118 AN: 2630

East Asian (EAS) AF: 0.0154 AC: 55 AN: 3567

South Asian (SAS) AF: 0.156 AC: 420 AN: 2689

European-Finnish (FIN) AF: 0.343 AC: 2025 AN: 5898

Middle Eastern (MID) AF: 0.264 AC: 57 AN: 216

European-Non Finnish (NFE) AF: 0.361 AC: 19061 AN: 52868

Other (OTH) AF: 0.282 AC: 422 AN: 1499

Alfa AF: 0.331 Hom.: 39406

Bravo AF: 0.282

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.23
DANN	Benign	0.64
PhyloP100		-2.8
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: rs17321050; hg19: chrX-9613099;