chr3-177047481-T-C

Position:

chr3-177047481-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000457928.7(TBL1XR1):c.766+5A>G variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 1,611,488 control chromosomes in the GnomAD database, including 35,897 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 3099 hom., cov: 32)

Exomes 𝑓: 0.20 ( 32798 hom. )

Consequence

TBL1XR1
ENST00000457928.7 splice_donor_5th_base, intron

Scores

Splicing: ADA: 0.00008531

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.276

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:

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

TBL1XR1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 3-177047481-T-C is Benign according to our data. Variant chr3-177047481-T-C is described in ClinVar as [Benign]. Clinvar id is 586783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBL1XR1	NM_024665.7 linkuse as main transcript	c.766+5A>G		splice_donor_5th_base_variant, intron_variant		ENST00000457928.7	NP_078941.2
TBL1XR1-AS1	NR_174966.1 linkuse as main transcript	n.518-153T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBL1XR1	ENST00000457928.7 linkuse as main transcript	c.766+5A>G		splice_donor_5th_base_variant, intron_variant		1	NM_024665.7	ENSP00000413251	P1
TBL1XR1-AS1	ENST00000617758.1 linkuse as main transcript	n.530-153T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

26343

AN:

152074

Hom.:

3093

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0506

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.218

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.497

Gnomad SAS

AF:

0.0803

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.173

GnomAD3 exomes

AF:

0.211

AC:

52232

AN:

247644

Hom.:

7023

AF XY:

0.203

AC XY:

27307

AN XY:

134370

show subpopulations

Gnomad AFR exome

AF:

0.0468

Gnomad AMR exome

AF:

0.225

Gnomad ASJ exome

AF:

0.168

Gnomad EAS exome

AF:

0.520

Gnomad SAS exome

AF:

0.0785

Gnomad FIN exome

AF:

0.257

Gnomad NFE exome

AF:

0.211

Gnomad OTH exome

AF:

0.215

GnomAD4 exome

AF:

0.202

AC:

294498

AN:

1459296

Hom.:

32798

Cov.:

AF XY:

0.198

AC XY:

143739

AN XY:

725936

show subpopulations

Gnomad4 AFR exome

AF:

0.0423

Gnomad4 AMR exome

AF:

0.222

Gnomad4 ASJ exome

AF:

0.169

Gnomad4 EAS exome

AF:

0.457

Gnomad4 SAS exome

AF:

0.0791

Gnomad4 FIN exome

AF:

0.253

Gnomad4 NFE exome

AF:

0.205

Gnomad4 OTH exome

AF:

0.195

GnomAD4 genome

AF:

0.173

AC:

26355

AN:

152192

Hom.:

3099

Cov.:

AF XY:

0.178

AC XY:

13233

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0505

Gnomad4 AMR

AF:

0.218

Gnomad4 ASJ

AF:

0.173

Gnomad4 EAS

AF:

0.498

Gnomad4 SAS

AF:

0.0798

Gnomad4 FIN

AF:

0.247

Gnomad4 NFE

AF:

0.207

Gnomad4 OTH

AF:

0.179

Alfa

AF:

0.198

Hom.:

6347

Bravo

AF:

0.170

Asia WGS

AF:

0.222

AC:

769

AN:

3476

EpiCase

AF:

0.205

EpiControl

AF:

0.204

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 20, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Pierpont syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.4

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000085

dbscSNV1_RF

Benign

0.0060

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