dbSNP rs71170848: TBL1XR1:c.1122+306_1122+325delGATGGATGGATGGATGGATG (chr3-177037772-TCATCCATCCATCCATCCATC-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_024665.7(TBL1XR1):c.1122+306_1122+325delGATGGATGGATGGATGGATG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00006 in 183,472 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000060 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

TBL1XR1
NM_024665.7 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.38

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 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: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 9 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	Effect	Exon Rank	Protein	UniProt
TBL1XR1	NM_024665.7	MANE Select	c.1122+306_1122+325delGATGGATGGATGGATGGATG	intron	N/A	NP_078941.2
TBL1XR1	NM_001321193.3		c.1122+306_1122+325delGATGGATGGATGGATGGATG	intron	N/A	NP_001308122.1	Q9BZK7
TBL1XR1	NM_001321194.3		c.1122+306_1122+325delGATGGATGGATGGATGGATG	intron	N/A	NP_001308123.1	Q9BZK7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TBL1XR1	ENST00000457928.7	TSL:1 MANE Select	c.1122+306_1122+325delGATGGATGGATGGATGGATG	intron	N/A	ENSP00000413251.3	Q9BZK7
TBL1XR1	ENST00000430069.5	TSL:1	c.1122+306_1122+325delGATGGATGGATGGATGGATG	intron	N/A	ENSP00000405574.1	Q9BZK7
TBL1XR1	ENST00000352800.10	TSL:5	c.1122+306_1122+325delGATGGATGGATGGATGGATG	intron	N/A	ENSP00000263964.11	Q9BZK7

Frequencies

GnomAD3 genomes

AF:

0.0000604

AC:

AN:

148904

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000175

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000672

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000579

AC:

AN:

34568

Hom.:

AF XY:

0.0000554

AC XY:

AN XY:

18040

show subpopulations

African (AFR)

AF:

0.00121

AC:

AN:

828

American (AMR)

AF:

0.000725

AC:

AN:

1380

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1090

East Asian (EAS)

AF:

0.00

AC:

AN:

1644

South Asian (SAS)

AF:

0.00

AC:

AN:

3462

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

148

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

22442

Other (OTH)

AF:

0.00

AC:

AN:

1994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000604

AC:

AN:

148904

Hom.:

Cov.:

AF XY:

0.0000552

AC XY:

AN XY:

72468

show subpopulations

African (AFR)

AF:

0.000175

AC:

AN:

39972

American (AMR)

AF:

0.0000672

AC:

AN:

14878

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3438

East Asian (EAS)

AF:

0.00

AC:

AN:

5010

South Asian (SAS)

AF:

0.00

AC:

AN:

4660

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10160

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67532

Other (OTH)

AF:

0.00

AC:

AN:

2042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

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:

0.00

Hom.:

130

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over