dbSNP rs61750378: TBL1XR1:p.Pro223Pro (chr3-177050030-T-C) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_024665.7(TBL1XR1):c.669A>G(p.Pro223Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00644 in 1,613,678 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0049 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0066 ( 36 hom. )

Consequence

TBL1XR1
NM_024665.7 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.565

Publications

4 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
Pierpont syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

TBL1XR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 3-177050030-T-C is Benign according to our data. Variant chr3-177050030-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 468538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.565 with no splicing effect.

BS2

High AC in GnomAd4 at 748 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024665.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBL1XR1	NM_024665.7	MANE Select	c.669A>G	p.Pro223Pro	synonymous	Exon 7 of 16	NP_078941.2
TBL1XR1	NM_001321193.3		c.669A>G	p.Pro223Pro	synonymous	Exon 7 of 16	NP_001308122.1	Q9BZK7
TBL1XR1	NM_001321194.3		c.669A>G	p.Pro223Pro	synonymous	Exon 8 of 17	NP_001308123.1	Q9BZK7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBL1XR1	ENST00000457928.7	TSL:1 MANE Select	c.669A>G	p.Pro223Pro	synonymous	Exon 7 of 16	ENSP00000413251.3	Q9BZK7
TBL1XR1	ENST00000430069.5	TSL:1	c.669A>G	p.Pro223Pro	synonymous	Exon 7 of 16	ENSP00000405574.1	Q9BZK7
TBL1XR1	ENST00000352800.10	TSL:5	c.669A>G	p.Pro223Pro	synonymous	Exon 6 of 15	ENSP00000263964.11	Q9BZK7

Frequencies

GnomAD3 genomes

AF:

0.00492

AC:

748

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00593

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00853

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00503

AC:

1250

AN:

248702

AF XY:

0.00469

show subpopulations

Gnomad AFR exome

AF:

0.00103

Gnomad AMR exome

AF:

0.000899

Gnomad ASJ exome

AF:

0.00527

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00755

Gnomad NFE exome

AF:

0.00849

Gnomad OTH exome

AF:

0.00514

GnomAD4 exome

AF:

0.00660

AC:

9640

AN:

1461402

Hom.:

Cov.:

AF XY:

0.00634

AC XY:

4610

AN XY:

726982

show subpopulations

African (AFR)

AF:

0.000657

AC:

AN:

33468

American (AMR)

AF:

0.00107

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00563

AC:

147

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00780

AC:

416

AN:

53306

Middle Eastern (MID)

AF:

0.000694

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00780

AC:

8674

AN:

1111728

Other (OTH)

AF:

0.00543

AC:

328

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

460

920

1381

1841

2301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

292

584

876

1168

1460

<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:

0.00491

AC:

748

AN:

152276

Hom.:

Cov.:

AF XY:

0.00449

AC XY:

334

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00116

AC:

AN:

41552

American (AMR)

AF:

0.00170

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00403

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00593

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00853

AC:

580

AN:

68010

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

117

156

195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00720

Hom.:

Bravo

AF:

0.00430

Asia WGS

AF:

0.000867

AC:

AN:

3476

EpiCase

AF:

0.00807

EpiControl

AF:

0.00706

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

Inborn genetic diseases (1)

not specified (1)

Pierpont syndrome (1)

Pierpont syndrome;C4310784:Intellectual disability, autosomal dominant 41 (1)

TBL1XR1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.0

(source)

DANN

Benign

0.75

PhyloP100

-0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over