3-177047481-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024665.7(TBL1XR1):c.766+5A>G variant causes a splice region, 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
NM_024665.7 splice_region, intron

Scores

Splicing: ADA: 0.00008531

Clinical Significance

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

Conservation

PhyloP100: -0.276

Publications

14 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
TBL1XR1	NM_024665.7 link	c.766+5A>G		splice_region_variant, intron_variant	Intron 8 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.766+5A>G		splice_region_variant, intron_variant	Intron 8 of 15	1	NM_024665.7	ENSP00000413251.3		Q9BZK7

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

GnomAD2 exomes

AF:

0.211

AC:

52232

AN:

247644

AF XY:

0.203

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 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

African (AFR)

AF:

0.0423

AC:

1414

AN:

33404

American (AMR)

AF:

0.222

AC:

9885

AN:

44582

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

4407

AN:

26062

East Asian (EAS)

AF:

0.457

AC:

18114

AN:

39620

South Asian (SAS)

AF:

0.0791

AC:

6806

AN:

86008

European-Finnish (FIN)

AF:

0.253

AC:

13500

AN:

53340

Middle Eastern (MID)

AF:

0.149

AC:

848

AN:

5706

European-Non Finnish (NFE)

AF:

0.205

AC:

227768

AN:

1110316

Other (OTH)

AF:

0.195

AC:

11756

AN:

60258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

11304

22608

33911

45215

56519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7776

15552

23328

31104

38880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.173

AC:

26355

AN:

152192

Hom.:

3099

Cov.:

AF XY:

0.178

AC XY:

13233

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0505

AC:

2098

AN:

41562

American (AMR)

AF:

0.218

AC:

3331

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

599

AN:

3466

East Asian (EAS)

AF:

0.498

AC:

2577

AN:

5178

South Asian (SAS)

AF:

0.0798

AC:

384

AN:

4814

European-Finnish (FIN)

AF:

0.247

AC:

2612

AN:

10582

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.207

AC:

14092

AN:

67986

Other (OTH)

AF:

0.179

AC:

379

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1074

2147

3221

4294

5368

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

278

556

834

1112

1390

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.190

Hom.:

8466

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

Jul 15, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 20, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Inborn genetic diseases

Benign:1

Jan 08, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Feb 04, 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

-0.53

CADD

Benign

9.4

(source)

DANN

Benign

0.77

PhyloP100

-0.28

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=62/38

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over