chr16-3026101-C-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_024339.5(THOC6):c.259C>T(p.Arg87Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000559 in 1,608,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
THOC6
NM_024339.5 stop_gained
NM_024339.5 stop_gained
Scores
2
2
3
Clinical Significance
Conservation
PhyloP100: 0.598
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 12 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 16-3026101-C-T is Pathogenic according to our data. Variant chr16-3026101-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 520614.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-3026101-C-T is described in Lovd as [Pathogenic]. Variant chr16-3026101-C-T is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THOC6 | NM_024339.5 | c.259C>T | p.Arg87Ter | stop_gained | 4/13 | ENST00000326266.13 | |
THOC6 | NM_001347704.2 | c.259C>T | p.Arg87Ter | stop_gained | 5/14 | ||
THOC6 | NM_001347703.2 | c.187C>T | p.Arg63Ter | stop_gained | 5/14 | ||
THOC6 | NM_001142350.3 | c.259C>T | p.Arg87Ter | stop_gained | 4/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THOC6 | ENST00000326266.13 | c.259C>T | p.Arg87Ter | stop_gained | 4/13 | 1 | NM_024339.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152150Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249292Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134688
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GnomAD4 exome AF: 0.00000549 AC: 8AN: 1456632Hom.: 0 Cov.: 38 AF XY: 0.00000138 AC XY: 1AN XY: 723686
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome Pathogenic:1Other:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 07, 2020 | - - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 09, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
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Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
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Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MutationTaster
Benign
A;A;A;A
Vest4
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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