rs797045019
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP5
The NM_001081550.2(THOC2):c.937C>T(p.Leu313Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. L313L) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 23)
Consequence
THOC2
NM_001081550.2 missense
NM_001081550.2 missense
Scores
4
9
4
Clinical Significance
Conservation
PhyloP100: 9.10
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 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, THOC2
PP5
?
Variant X-123668239-G-A is Pathogenic according to our data. Variant chrX-123668239-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 208524.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THOC2 | NM_001081550.2 | c.937C>T | p.Leu313Phe | missense_variant | 10/39 | ENST00000245838.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THOC2 | ENST00000245838.13 | c.937C>T | p.Leu313Phe | missense_variant | 10/39 | 5 | NM_001081550.2 | P1 | |
THOC2 | ENST00000355725.8 | c.937C>T | p.Leu313Phe | missense_variant | 10/39 | 5 | P1 | ||
THOC2 | ENST00000491737.5 | c.592C>T | p.Leu198Phe | missense_variant | 6/34 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Cov.: 27
GnomAD4 exome
Cov.:
27
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
X-linked intellectual disability-short stature-overweight syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 06, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Pathogenic
DEOGEN2
Benign
T;T;T
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;.;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
T;T;T
Polyphen
D;D;.
Vest4
MutPred
Gain of ubiquitination at K312 (P = 0.0918);Gain of ubiquitination at K312 (P = 0.0918);.;
MVP
MPC
ClinPred
D
GERP RS
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