8-91071227-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_016023.5(OTUD6B):c.172G>A(p.Glu58Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,884 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 1 hom. )
Consequence
OTUD6B
NM_016023.5 missense
NM_016023.5 missense
Scores
1
8
6
Clinical Significance
Conservation
PhyloP100: 9.24
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2766509).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTUD6B | NM_016023.5 | c.172G>A | p.Glu58Lys | missense_variant | 2/7 | ENST00000404789.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTUD6B | ENST00000404789.8 | c.172G>A | p.Glu58Lys | missense_variant | 2/7 | 1 | NM_016023.5 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152196Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000319 AC: 8AN: 251104Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135718
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GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461570Hom.: 1 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727076
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GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152314Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5AN XY: 74480
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 29, 2020 | The c.262G>A (p.E88K) alteration is located in exon 2 (coding exon 2) of the OTUD6B gene. This alteration results from a G to A substitution at nucleotide position 262, causing the glutamic acid (E) at amino acid position 88 to be replaced by a lysine (K). Based on data from the Genome Aggregation Database (gnomAD) database, the OTUD6B c.262G>A alteration was observed in 0.004% (11/282486) of total alleles studied, with a frequency of 0.04% (10/24966) in the African subpopulation. This amino acid position is not well conserved in available vertebrate species. The in silico prediction for the p.E88K alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;T
Polyphen
0.39
.;.;B
Vest4
MutPred
0.38
.;.;Gain of MoRF binding (P = 0.0068);
MVP
MPC
0.13
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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