GeneBe

3-177026243-GA-G

Variant names:

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

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
TBL1XR1NM_024665.7 linkc.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
TBL1XR1ENST00000457928.7 linkc.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.:
22
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
0
4544
9088
13632
18176
22720
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
1146
2292
3438
4584
5730
<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:
0.265
AC:
38889
AN:
146830
Hom.:
5429
Cov.:
22
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:
58
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
0
1400
2800
4200
5600
7000
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
388
776
1164
1552
1940
<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:
0.0897
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)

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

Other links and lift over

dbSNP: rs3046447; hg19: chr3-176744031; COSMIC: COSV107527173; COSMIC: COSV107527173; API