dbSNP rs144060569: TBL1XR1:c.1416+14A>G (chr3-177032957-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024665.7(TBL1XR1):c.1416+14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,533,390 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 34 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 21 hom. )

Consequence

TBL1XR1
NM_024665.7 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0690

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 3-177032957-T-C is Benign according to our data. Variant chr3-177032957-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 445304.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0106 (1610/152292) while in subpopulation AFR AF= 0.0365 (1516/41548). AF 95% confidence interval is 0.035. There are 34 homozygotes in gnomad4. There are 736 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1610 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBL1XR1	NM_024665.7 link	c.1416+14A>G		intron_variant	Intron 14 of 15	ENST00000457928.7	NP_078941.2	Q9BZK7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBL1XR1	ENST00000457928.7 link	c.1416+14A>G		intron_variant	Intron 14 of 15	1	NM_024665.7	ENSP00000413251.3		Q9BZK7

Frequencies

GnomAD3 genomes

AF:

0.0106

AC:

1609

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0365

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00292

AC:

632

AN:

216532

Hom.:

AF XY:

0.00225

AC XY:

265

AN XY:

117734

show subpopulations

Gnomad AFR exome

AF:

0.0357

Gnomad AMR exome

AF:

0.00212

Gnomad ASJ exome

AF:

0.00256

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000831

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000264

Gnomad OTH exome

AF:

0.00178

GnomAD4 exome

AF:

0.00120

AC:

1662

AN:

1381098

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

752

AN XY:

682620

show subpopulations

Gnomad4 AFR exome

AF:

0.0376

Gnomad4 AMR exome

AF:

0.00219

Gnomad4 ASJ exome

AF:

0.00325

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000539

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000169

Gnomad4 OTH exome

AF:

0.00243

GnomAD4 genome

AF:

0.0106

AC:

1610

AN:

152292

Hom.:

Cov.:

AF XY:

0.00988

AC XY:

736

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0365

Gnomad4 AMR

AF:

0.00294

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00471

Hom.:

Bravo

AF:

0.0120

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 08, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Pierpont syndrome

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.5

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over