chr16-3026141-G-A
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_024339.5(THOC6):c.299G>A(p.Trp100Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
THOC6
NM_024339.5 stop_gained
NM_024339.5 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 6.53
Genes affected
THOC6 (HGNC:28369): (THO complex subunit 6) This gene encodes a subunit of the multi-protein THO complex, which is involved in coordination between transcription and mRNA processing. The THO complex is a component of the TREX (transcription/export) complex, which is involved in transcription and export of mRNAs. A missense mutation in this gene is associated with a neurodevelopmental disorder called Beaulieu-Boycott-Innes syndrome. [provided by RefSeq, Dec 2016]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 16-3026141-G-A is Pathogenic according to our data. Variant chr16-3026141-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 633694.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THOC6 | NM_024339.5 | c.299G>A | p.Trp100Ter | stop_gained | 4/13 | ENST00000326266.13 | |
THOC6 | NM_001347704.2 | c.299G>A | p.Trp100Ter | stop_gained | 5/14 | ||
THOC6 | NM_001347703.2 | c.227G>A | p.Trp76Ter | stop_gained | 5/14 | ||
THOC6 | NM_001142350.3 | c.299G>A | p.Trp100Ter | stop_gained | 4/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THOC6 | ENST00000326266.13 | c.299G>A | p.Trp100Ter | stop_gained | 4/13 | 1 | NM_024339.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 38
GnomAD4 exome
Cov.:
38
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Sbielas Lab-Department of Human Genetics University of Michigan, University of Michigan Medical School | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A;A;A
Vest4
GERP RS
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