Genetic Variant NM_024665.7:c.1518+129delT (chr3-177026243-GA-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_024665.7(TBL1XR1):c.1518+129delT 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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.787

Publications

0 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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
intellectual disability, autosomal dominant 41
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
Pierpont syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

TBL1XR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TBL1XR1	NM_024665.7 link	c.1518+129delT		intron_variant	Intron 15 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.1518+129delT		intron_variant	Intron 15 of 15	1	NM_024665.7	ENSP00000413251.3		Q9BZK7

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

38824

AN:

146740

Hom.:

5408

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.364

AC:

3425

AN:

9400

American (AMR)

AF:

0.309

AC:

3203

AN:

10362

Ashkenazi Jewish (ASJ)

AF:

0.295

AC:

3735

AN:

12642

East Asian (EAS)

AF:

0.475

AC:

10551

AN:

22232

South Asian (SAS)

AF:

0.200

AC:

6654

AN:

33306

European-Finnish (FIN)

AF:

0.329

AC:

10428

AN:

31742

Middle Eastern (MID)

AF:

0.251

AC:

485

AN:

1930

European-Non Finnish (NFE)

AF:

0.275

AC:

79523

AN:

288886

Other (OTH)

AF:

0.303

AC:

6712

AN:

22166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

4544

9088

13632

18176

22720

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.265

AC:

38889

AN:

146830

Hom.:

5429

Cov.:

AF XY:

0.268

AC XY:

19108

AN XY:

71378

show subpopulations

African (AFR)

AF:

0.331

AC:

13326

AN:

40302

American (AMR)

AF:

0.259

AC:

3834

AN:

14788

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

738

AN:

3396

East Asian (EAS)

AF:

0.503

AC:

2551

AN:

5070

South Asian (SAS)

AF:

0.115

AC:

532

AN:

4624

European-Finnish (FIN)

AF:

0.281

AC:

2607

AN:

9286

Middle Eastern (MID)

AF:

0.203

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.219

AC:

14482

AN:

66176

Other (OTH)

AF:

0.248

AC:

499

AN:

2016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1400

2800

4200

5600

7000

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0897

Hom.:

152

Bravo

AF:

0.262

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 10, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.79

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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NM_024665.7:c.1518+129delT

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