chr16-3025709-CAG-C
Position:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1_StrongPM2PP3_ModeratePP5_Moderate
The ENST00000574549.5(THOC6):c.-29_-28del variant causes a splice acceptor change. The variant allele was found at a frequency of 0.00000186 in 1,613,542 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
THOC6
ENST00000574549.5 splice_acceptor
ENST00000574549.5 splice_acceptor
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.02
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
Splicing variant, NOT destroyed by nmd, known LOF gene, truncates exone, which is 0.1163522 fraction of the gene. Cryptic splice site detected, with MaxEntScore 3.5, offset of 0 (no position change), new splice context is: cagtctttccctgcagacAGgtg. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
Variant 16-3025709-CAG-C is Pathogenic according to our data. Variant chr16-3025709-CAG-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1325193.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THOC6 | NM_024339.5 | c.44_45del | p.Glu15GlyfsTer51 | frameshift_variant, splice_region_variant | 2/13 | ENST00000326266.13 | |
THOC6 | NM_001347703.2 | c.-29_-28del | splice_acceptor_variant | ||||
THOC6 | NM_001142350.3 | c.44_45del | p.Glu15GlyfsTer51 | frameshift_variant, splice_region_variant | 2/12 | ||
THOC6 | NM_001347704.2 | c.44_45del | p.Glu15GlyfsTer51 | frameshift_variant, splice_region_variant | 3/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THOC6 | ENST00000326266.13 | c.44_45del | p.Glu15GlyfsTer51 | frameshift_variant, splice_region_variant | 2/13 | 1 | NM_024339.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
2
AN:
152220
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251288Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135790
GnomAD3 exomes
AF:
AC:
3
AN:
251288
Hom.:
AF XY:
AC XY:
1
AN XY:
135790
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461322Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 727004
GnomAD4 exome
AF:
AC:
1
AN:
1461322
Hom.:
AF XY:
AC XY:
0
AN XY:
727004
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74360
GnomAD4 genome
AF:
AC:
2
AN:
152220
Hom.:
Cov.:
33
AF XY:
AC XY:
2
AN XY:
74360
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
THOC6-related developmental delay-microcephaly-facial dysmorphism syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 28, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 5
Find out detailed SpliceAI scores and Pangolin per-transcript scores at