8-91070465-A-G

Variant names:

• chr8-91070465-A-G
• rs1431292062
• NM_016023.5:c.81A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_016023.5(OTUD6B):​c.81A>G​(p.Gln27Gln) variant causes a splice region, synonymous 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. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OTUD6B NM_016023.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.7578
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.31
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 8-91070465-A-G is Benign according to our data. Variant chr8-91070465-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2658683.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.31 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD6B	NM_016023.5	MANE Select	c.81A>G	p.Gln27Gln	splice_region synonymous	Exon 1 of 7	NP_057107.4
	OTUD6B	NM_001286745.3		c.-363A>G		splice_region	Exon 1 of 8	NP_001273674.1	Q8N6M0-2
	OTUD6B	NM_001416022.1		c.81A>G	p.Gln27Gln	splice_region synonymous	Exon 1 of 6	NP_001402951.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD6B	ENST00000404789.8	TSL:1 MANE Select	c.81A>G	p.Gln27Gln	splice_region synonymous	Exon 1 of 7	ENSP00000384190.4	Q8N6M0-1
	OTUD6B	ENST00000285420.8	TSL:1	c.171A>G	p.Gln57Gln	splice_region synonymous	Exon 1 of 7	ENSP00000285420.4	A0A087X0W9
	OTUD6B	ENST00000617869.4	TSL:1	c.171A>G	p.Gln57Gln	splice_region synonymous	Exon 1 of 7	ENSP00000483706.1	A0A087X0W9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	19
DANN	Benign	0.84
PhyloP100		1.3
PromoterAI		-0.054	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.76
dbscSNV1_RF	Benign	0.51
SpliceAI score (max)		0.010		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: rs1431292062; hg19: chr8-92082693;