X-123613538-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001081550.2(THOC2):c.4538A>G(p.Lys1513Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 22)
Consequence
THOC2
NM_001081550.2 missense
NM_001081550.2 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 6.55
Genes affected
THOC2 (HGNC:19073): (THO complex subunit 2) The TREX multiprotein complex binds specifically to spliced mRNAs to facilitate mRNA export. The protein encoded by this gene is a member of the THO complex, a subset of the TREX complex. The encoded protein interacts with the THOC1 protein.[provided by RefSeq, Jun 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), THOC2. . Gene score misZ 5.5258 (greater than the threshold 3.09). GenCC has associacion of gene with X-linked intellectual disability-short stature-overweight syndrome.
BP4
Computational evidence support a benign effect (MetaRNN=0.2518567).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
THOC2 | NM_001081550.2 | c.4538A>G | p.Lys1513Arg | missense_variant | 36/39 | ENST00000245838.13 | NP_001075019.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
THOC2 | ENST00000245838.13 | c.4538A>G | p.Lys1513Arg | missense_variant | 36/39 | 5 | NM_001081550.2 | ENSP00000245838.8 | ||
THOC2 | ENST00000355725.8 | c.4538A>G | p.Lys1513Arg | missense_variant | 36/39 | 5 | ENSP00000347959.4 | |||
THOC2 | ENST00000491737.5 | c.4193A>G | p.Lys1398Arg | missense_variant | 32/34 | 5 | ENSP00000419795.1 | |||
THOC2 | ENST00000441692.5 | c.920A>G | p.Lys307Arg | missense_variant | 7/10 | 5 | ENSP00000415211.1 | |||
THOC2 | ENST00000448128.5 | c.323A>G | p.Lys108Arg | missense_variant | 6/9 | 5 | ENSP00000397317.1 | |||
THOC2 | ENST00000416618.5 | c.305A>G | p.Lys102Arg | missense_variant | 5/8 | 5 | ENSP00000415244.1 | |||
THOC2 | ENST00000455053.5 | c.17A>G | p.Lys6Arg | missense_variant | 1/4 | 3 | ENSP00000402168.1 | |||
THOC2 | ENST00000432353.5 | n.*780A>G | non_coding_transcript_exon_variant | 6/9 | 1 | ENSP00000415947.1 | ||||
THOC2 | ENST00000432353.5 | n.*780A>G | 3_prime_UTR_variant | 6/9 | 1 | ENSP00000415947.1 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 genomes
Cov.:
22
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 22
GnomAD4 genome
Cov.:
22
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 07, 2024 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;.;.;T;T
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;.;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.;L;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;D;N;N;N
REVEL
Uncertain
Sift
Benign
T;.;D;T;T;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
B;.;.;.;B;.
Vest4
MutPred
Loss of ubiquitination at K1513 (P = 0.0027);.;.;.;Loss of ubiquitination at K1513 (P = 0.0027);.;
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
Publications
No publications associated with this variant yet.