rs61750378
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_024665.7(TBL1XR1):āc.669A>Gā(p.Pro223=) 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 (ā ā ).
Frequency
Genomes: š 0.0049 ( 3 hom., cov: 32)
Exomes š: 0.0066 ( 36 hom. )
Consequence
TBL1XR1
NM_024665.7 synonymous
NM_024665.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.565
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id 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.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBL1XR1 | NM_024665.7 | c.669A>G | p.Pro223= | synonymous_variant | 7/16 | ENST00000457928.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBL1XR1 | ENST00000457928.7 | c.669A>G | p.Pro223= | synonymous_variant | 7/16 | 1 | NM_024665.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00492 AC: 748AN: 152158Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00503 AC: 1250AN: 248702Hom.: 3 AF XY: 0.00469 AC XY: 633AN XY: 134948
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GnomAD4 exome AF: 0.00660 AC: 9640AN: 1461402Hom.: 36 Cov.: 31 AF XY: 0.00634 AC XY: 4610AN XY: 726982
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GnomAD4 genome ? AF: 0.00491 AC: 748AN: 152276Hom.: 3 Cov.: 32 AF XY: 0.00449 AC XY: 334AN XY: 74470
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 27, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | TBL1XR1: BP4, BP7, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 14, 2018 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 19, 2019 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 27, 2016 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Pierpont syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Pierpont syndrome;C4310784:Intellectual disability, autosomal dominant 41 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 10, 2022 | - - |
TBL1XR1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 27, 2024 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at