8-91070322-T-G

Variant names:

• chr8-91070322-T-G
• rs745687110
• ENST00000285420.8:c.28T>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000285420.8(OTUD6B):​c.28T>G​(p.Trp10Gly) 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. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W10R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: OTUD6B ENST00000285420.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17368105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTUD6B	NM_016023.5	c.-63T>G		upstream_gene_variant		ENST00000404789.8	NP_057107.4
OTUD6B	NM_001416022.1	c.-63T>G		upstream_gene_variant			NP_001402951.1
OTUD6B	NM_001286745.3	c.-506T>G		upstream_gene_variant			NP_001273674.1
OTUD6B	XM_047421864.1	c.-63T>G		upstream_gene_variant			XP_047277820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTUD6B	ENST00000404789.8	c.-63T>G		upstream_gene_variant		1	NM_016023.5	ENSP00000384190.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.0098	T;T
Eigen	Benign	0.055
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.41	T;.
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.060	.;N
REVEL	Benign	0.080
Sift	Benign	0.28	.;T
Sift4G	Uncertain	0.026	D;D
Vest4		0.33
MutPred		0.45		Gain of disorder (P = 0.0019);Gain of disorder (P = 0.0019);
MVP		0.39
MPC		0.021
ClinPred		0.61	D
GERP RS		5.7
gMVP		0.11

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

LitVar

Other links and lift over

dbSNP: rs745687110; hg19: chr8-92082550;