3-177026243-GA-G

Position:

• chr3-177026243-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_024665.7(TBL1XR1):​c.1518+129del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 579,496 control chromosomes in the GnomAD database, including 15,161 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (5429 hom., cov: 22)
  • Exomes 𝑓: 0.29 (9732 hom.)
• Consequence: TBL1XR1 NM_024665.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.787

Genes affected

TBL1XR1 (HGNC:29529): (TBL1X/Y related 1) This gene is a member of the WD40 repeat-containing gene family and shares sequence similarity with transducin (beta)-like 1X-linked (TBL1X). The protein encoded by this gene is thought to be a component of both nuclear receptor corepressor (N-CoR) and histone deacetylase 3 (HDAC 3) complexes, and is required for transcriptional activation by a variety of transcription factors. Mutations in these gene have been associated with some autism spectrum disorders, and one finding suggests that haploinsufficiency of this gene may be a cause of intellectual disability with dysmorphism. Mutations in this gene as well as recurrent translocations involving this gene have also been observed in some tumors. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-177026243-GA-G is Benign according to our data. Variant chr3-177026243-GA-G is described in ClinVar as [Benign]. Clinvar id is 1236683.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBL1XR1	NM_024665.7	c.1518+129del		intron_variant		ENST00000457928.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBL1XR1	ENST00000457928.7	c.1518+129del		intron_variant		1	NM_024665.7	P1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 38824 AN: 146740 Hom.: 5408 Cov.: 22

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.242

GnomAD4 exome AF: 0.288 AC: 124716 AN: 432666 Hom.: 9732 AF XY: 0.285 AC XY: 65172 AN XY: 228516

Gnomad4 AFR exome AF: 0.364

Gnomad4 AMR exome AF: 0.309

Gnomad4 ASJ exome AF: 0.295

Gnomad4 EAS exome AF: 0.475

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.329

Gnomad4 NFE exome AF: 0.275

Gnomad4 OTH exome AF: 0.303

GnomAD4 genome AF: 0.265 AC: 38889 AN: 146830 Hom.: 5429 Cov.: 22 AF XY: 0.268 AC XY: 19108 AN XY: 71378

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.248

Bravo AF: 0.262

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs3046447; hg19: chr3-176744031;