chr3-177037772-TCATC-T

Position:

• chr3-177037772-TCATC-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_024665.7(TBL1XR1):​c.1122+322_1122+325del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 183,534 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (4 hom., cov: 0)
  • Exomes 𝑓: 0.0021 (1 hom.)
• Consequence: TBL1XR1 NM_024665.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.244

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]

TBL1XR1-AS1 (HGNC:41243): (TBL1XR1 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 3-177037772-TCATC-T is Benign according to our data. Variant chr3-177037772-TCATC-T is described in ClinVar as [Benign]. Clinvar id is 2654284.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 491 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBL1XR1	NM_024665.7	c.1122+322_1122+325del		intron_variant		ENST00000457928.7
TBL1XR1-AS1	NR_174966.1	n.340+61_340+64del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBL1XR1	ENST00000457928.7	c.1122+322_1122+325del		intron_variant		1	NM_024665.7	P1
TBL1XR1-AS1	ENST00000617758.1	n.340+61_340+64del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00329 AC: 490 AN: 148898 Hom.: 4 Cov.: 0

Gnomad AFR AF: 0.00838

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00195

Gnomad ASJ AF: 0.000582

Gnomad EAS AF: 0.00140

Gnomad SAS AF: 0.0144

Gnomad FIN AF: 0.000886

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000592

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00209 AC: 72 AN: 34518 Hom.: 1 AF XY: 0.00261 AC XY: 47 AN XY: 18020

Gnomad4 AFR exome AF: 0.0121

Gnomad4 AMR exome AF: 0.00218

Gnomad4 ASJ exome AF: 0.000919

Gnomad4 EAS exome AF: 0.000611

Gnomad4 SAS exome AF: 0.00780

Gnomad4 FIN exome AF: 0.000634

Gnomad4 NFE exome AF: 0.00125

Gnomad4 OTH exome AF: 0.000503

GnomAD4 genome AF: 0.00329 AC: 491 AN: 149016 Hom.: 4 Cov.: 0 AF XY: 0.00355 AC XY: 258 AN XY: 72592

Gnomad4 AFR AF: 0.00838

Gnomad4 AMR AF: 0.00195

Gnomad4 ASJ AF: 0.000582

Gnomad4 EAS AF: 0.00140

Gnomad4 SAS AF: 0.0144

Gnomad4 FIN AF: 0.000886

Gnomad4 NFE AF: 0.000592

Gnomad4 OTH AF: 0.00

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

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

TBL1XR1: BS1, BS2 -

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: rs71170848; hg19: chr3-176755560;