rs759317757
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_016023.5(OTUD6B):c.379_383delTTAAC(p.Leu127ArgfsTer8) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,444,836 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
OTUD6B
NM_016023.5 frameshift
NM_016023.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.72
Publications
1 publications found
Genes affected
OTUD6B (HGNC:24281): (OTU deubiquitinase 6B) This gene encodes a member of the ovarian tumor domain (OTU)-containing subfamily of deubiquitinating enzymes. Deubiquitinating enzymes are primarily involved in removing ubiquitin from proteins targeted for degradation. This protein may function as a negative regulator of the cell cycle in B cells. [provided by RefSeq, Nov 2013]
OTUD6B Gene-Disease associations (from GenCC):
- intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomaliesInheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 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 8-91078415-AAACTT-A is Pathogenic according to our data. Variant chr8-91078415-AAACTT-A is described in ClinVar as Pathogenic. ClinVar VariationId is 375702.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_016023.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| OTUD6B | NM_016023.5 | MANE Select | c.379_383delTTAAC | p.Leu127ArgfsTer8 | frameshift | Exon 4 of 7 | NP_057107.4 | ||
| OTUD6B | NM_001416022.1 | c.298_302delTTAAC | p.Leu100ArgfsTer8 | frameshift | Exon 3 of 6 | NP_001402951.1 | |||
| OTUD6B | NM_001286745.3 | c.76_80delTTAAC | p.Leu26ArgfsTer8 | frameshift | Exon 5 of 8 | NP_001273674.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| OTUD6B | ENST00000404789.8 | TSL:1 MANE Select | c.379_383delTTAAC | p.Leu127ArgfsTer8 | frameshift | Exon 4 of 7 | ENSP00000384190.4 | ||
| OTUD6B | ENST00000285420.8 | TSL:1 | c.469_473delTTAAC | p.Leu157ArgfsTer8 | frameshift | Exon 4 of 7 | ENSP00000285420.4 | ||
| OTUD6B | ENST00000617869.4 | TSL:1 | c.469_473delTTAAC | p.Leu157ArgfsTer8 | frameshift | Exon 4 of 7 | ENSP00000483706.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00 AC: 0AN: 222850 AF XY: 0.00
GnomAD2 exomes
AF:
AC:
0
AN:
222850
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000138 AC: 2AN: 1444836Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 716914 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1444836
Hom.:
AF XY:
AC XY:
0
AN XY:
716914
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33112
American (AMR)
AF:
AC:
0
AN:
42270
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25712
East Asian (EAS)
AF:
AC:
0
AN:
39220
South Asian (SAS)
AF:
AC:
0
AN:
83424
European-Finnish (FIN)
AF:
AC:
0
AN:
52552
Middle Eastern (MID)
AF:
AC:
0
AN:
5744
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1102986
Other (OTH)
AF:
AC:
1
AN:
59816
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions as Germline
Significance:Pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Epilepsy;C0432072:Dysmorphic features;C3714756:Intellectual disability (1)
1
-
-
Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies (1)
1
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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