rs1236755685

Variant names:

• chrX-9688147-C-A
• rs1236755685
• NM_005647.4:c.488C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-9688147-C-A
• chrX-9688147-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_005647.4(TBL1X):​c.488C>A​(p.Ala163Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000736 in 1,086,559 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000074 (0 hom. 4 hem.)
• Consequence: TBL1X NM_005647.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.57

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

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17746267).
• BS2: High Hemizygotes in GnomAdExome4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBL1X	NM_005647.4	c.488C>A	p.Ala163Glu	missense_variant	Exon 7 of 18	ENST00000645353.2	NP_005638.1
TBL1X	NM_001139466.1	c.488C>A	p.Ala163Glu	missense_variant	Exon 7 of 18		NP_001132938.1
TBL1X	NM_001139467.1	c.335C>A	p.Ala112Glu	missense_variant	Exon 6 of 17		NP_001132939.1
TBL1X	NM_001139468.1	c.335C>A	p.Ala112Glu	missense_variant	Exon 7 of 18		NP_001132940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBL1X	ENST00000645353.2	c.488C>A	p.Ala163Glu	missense_variant	Exon 7 of 18		NM_005647.4	ENSP00000496215.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000736 AC: 8 AN: 1086559 Hom.: 0 Cov.: 32 AF XY: 0.0000113 AC XY: 4 AN XY: 354971

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000189

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000837

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Benign	0.50
DEOGEN2	Benign	0.21	.;T;.;T;T;T;T;.;.
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D;D;.;.;.;.;.;T;D
M_CAP	Benign	0.048	D
MetaRNN	Benign	0.13	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	.;L;.;L;L;L;L;.;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.10	N;N;N;N;.;.;.;.;.
REVEL	Benign	0.15
Sift	Benign	0.95	T;T;T;T;.;.;.;.;.
Sift4G	Benign	0.91	T;T;T;T;.;.;.;.;.
Polyphen		0.69	.;P;.;P;P;P;P;.;.
Vest4		0.41
MutPred		0.30		.;Gain of relative solvent accessibility (P = 0.09);.;Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);.;.;
MVP		0.69
MPC		0.85
ClinPred		0.20	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.45

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

LitVar

Other links and lift over

dbSNP: rs1236755685; hg19: chrX-9656187;