rs1812655898

Variant names:

• chr8-91070310-A-G
• rs1812655898
• ENST00000285420.8:c.16A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The ENST00000285420.8(OTUD6B):​c.16A>G​(p.Arg6Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R6S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OTUD6B ENST00000285420.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.90
• Publications: 0 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-AS1 (HGNC:50466): (OTUD6B antisense RNA 1 (head to head))

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 4 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.29632 (below the threshold of 3.09). Trascript score misZ: -0.53276 (below the threshold of 3.09). GenCC associations: The gene is linked to intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies.
• BP4: Computational evidence support a benign effect (MetaRNN=0.22618607).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000285420.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD6B	NM_016023.5	MANE Select	c.-75A>G		upstream_gene	N/A	NP_057107.4
	OTUD6B	NM_001416022.1		c.-75A>G		upstream_gene	N/A	NP_001402951.1
	OTUD6B	NM_001286745.3		c.-518A>G		upstream_gene	N/A	NP_001273674.1	Q8N6M0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD6B	ENST00000285420.8	TSL:1	c.16A>G	p.Arg6Gly	missense	Exon 1 of 7	ENSP00000285420.4	A0A087X0W9
	OTUD6B	ENST00000617869.4	TSL:1	c.16A>G	p.Arg6Gly	missense	Exon 1 of 7	ENSP00000483706.1	A0A087X0W9
	OTUD6B	ENST00000910621.1		c.-75A>G		5_prime_UTR	Exon 1 of 7	ENSP00000580680.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.74	T
PhyloP100		3.9
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.083
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0	D
Vest4		0.33
MutPred		0.36		Loss of sheet (P = 0.0043)
MVP		0.43
MPC		0.020
ClinPred		0.96	D
GERP RS		5.5
PromoterAI		0.043	Neutral
gMVP		0.16
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs1812655898; hg19: chr8-92082538; COSMIC: COSV53443028; COSMIC: COSV53443028;