rs1553817638
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1PM2PP2BP4
The NM_024665.7(TBL1XR1):c.130G>A(p.Val44Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
TBL1XR1
NM_024665.7 missense
NM_024665.7 missense
Scores
2
4
12
Clinical Significance
Conservation
PhyloP100: 7.91
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 Uncertain_significance. Variant got 4 ACMG points.
PM1
?
In a domain F-box-like (size 45) in uniprot entity TBL1R_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_024665.7
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, TBL1XR1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.38728446).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TBL1XR1 | NM_024665.7 | c.130G>A | p.Val44Ile | missense_variant | 4/16 | ENST00000457928.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TBL1XR1 | ENST00000457928.7 | c.130G>A | p.Val44Ile | missense_variant | 4/16 | 1 | NM_024665.7 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461416Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726996
GnomAD4 exome
AF:
AC:
3
AN:
1461416
Hom.:
Cov.:
31
AF XY:
AC XY:
3
AN XY:
726996
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 30, 2017 | - - |
Pierpont syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 23, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 521844). This variant has not been reported in the literature in individuals affected with TBL1XR1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 44 of the TBL1XR1 protein (p.Val44Ile). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;.;T;T;T;T;T;T;.;.;T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;.;.;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;N;.;.;N;.;.;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;.;.;T;.;.;T;T;T;T;T
Sift4G
Benign
T;T;.;.;.;.;T;.;.;.;.;.;.;.
Polyphen
D;D;.;.;.;.;.;.;.;.;.;.;.;.
Vest4
MutPred
Gain of catalytic residue at P46 (P = 0.0625);Gain of catalytic residue at P46 (P = 0.0625);Gain of catalytic residue at P46 (P = 0.0625);Gain of catalytic residue at P46 (P = 0.0625);Gain of catalytic residue at P46 (P = 0.0625);.;Gain of catalytic residue at P46 (P = 0.0625);Gain of catalytic residue at P46 (P = 0.0625);Gain of catalytic residue at P46 (P = 0.0625);Gain of catalytic residue at P46 (P = 0.0625);Gain of catalytic residue at P46 (P = 0.0625);Gain of catalytic residue at P46 (P = 0.0625);Gain of catalytic residue at P46 (P = 0.0625);Gain of catalytic residue at P46 (P = 0.0625);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at