8-91070399-G-C

Position:

• chr8-91070399-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_016023.5(OTUD6B):​c.15G>C​(p.Leu5Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OTUD6B NM_016023.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 1.77

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-AS1 (HGNC:50466): (OTUD6B antisense RNA 1 (head to head))

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM1: In a chain Deubiquitinase OTUD6B (size 292) in uniprot entity OTU6B_HUMAN there are 5 pathogenic changes around while only 2 benign (71%) in NM_016023.5
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14739135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTUD6B	NM_016023.5	c.15G>C	p.Leu5Phe	missense_variant	1/7	ENST00000404789.8
OTUD6B	NM_001416022.1	c.15G>C	p.Leu5Phe	missense_variant	1/6
OTUD6B	XM_047421864.1	c.15G>C	p.Leu5Phe	missense_variant	1/4
OTUD6B	NM_001286745.3	c.-429G>C		5_prime_UTR_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTUD6B	ENST00000404789.8	c.15G>C	p.Leu5Phe	missense_variant	1/7	1	NM_016023.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

OTUD6B-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 23, 2023

The OTUD6B c.105G>C variant is predicted to result in the amino acid substitution p.Leu35Phe. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.031	T;T;T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.72	T;.;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Uncertain	-0.00040	T
MutationAssessor	Benign	1.8	.;.;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.2	.;N;.
REVEL	Benign	0.18
Sift	Benign	0.033	.;D;.
Sift4G	Benign	0.12	T;T;T
Polyphen		0.26	.;.;B
Vest4		0.15
MutPred		0.20		.;.;Gain of loop (P = 0.069);
MVP		0.98
MPC		0.032
ClinPred		0.25	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.045
gMVP		0.027

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-92082627;