Genetic Variant TBL1XR1:c.1518+126_1518+129delTTTT (chr3-177026243-GAAAA-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024665.7(TBL1XR1):c.1518+126_1518+129delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000488 in 615,242 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 22)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

TBL1XR1
NM_024665.7 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.131

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBL1XR1	NM_024665.7 link	c.1518+126_1518+129delTTTT		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+126_1518+129delTTTT		intron_variant	Intron 15 of 15	1	NM_024665.7	ENSP00000413251.3		Q9BZK7

Frequencies

GnomAD3 genomes

AF:

0.00000681

AC:

AN:

146870

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000427

AC:

AN:

468372

Hom.:

AF XY:

0.00000806

AC XY:

AN XY:

248114

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

9984

American (AMR)

AF:

0.00

AC:

AN:

11206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13918

East Asian (EAS)

AF:

0.00

AC:

AN:

23372

South Asian (SAS)

AF:

0.00

AC:

AN:

37308

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34190

Middle Eastern (MID)

AF:

0.000469

AC:

AN:

2132

European-Non Finnish (NFE)

AF:

0.00000320

AC:

AN:

312080

Other (OTH)

AF:

0.00

AC:

AN:

24182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000681

AC:

AN:

146870

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71348

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40220

American (AMR)

AF:

0.00

AC:

AN:

14776

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3398

East Asian (EAS)

AF:

0.00

AC:

AN:

5090

South Asian (SAS)

AF:

0.00

AC:

AN:

4634

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9326

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000151

AC:

AN:

66234

Other (OTH)

AF:

0.00

AC:

AN:

1996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

152

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.13

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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chr3-177026243-GAAAA-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over