rs377765758

Variant names:

• chr8-91071158-A-G
• rs377765758
• NM_016023.5:c.103A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-91071158-A-G
• chr8-91071158-A-T

Variant summary

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

The NM_016023.5(OTUD6B):​c.103A>G​(p.Asn35Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,840 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OTUD6B NM_016023.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.61

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTUD6B	NM_016023.5	c.103A>G	p.Asn35Asp	missense_variant	Exon 2 of 7	ENST00000404789.8	NP_057107.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTUD6B	ENST00000404789.8	c.103A>G	p.Asn35Asp	missense_variant	Exon 2 of 7	1	NM_016023.5	ENSP00000384190.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250236 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135246

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460840 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726698

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T;T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D;.;D
M_CAP	Uncertain	0.26	D
MetaRNN	Uncertain	0.68	D;D;D
MetaSVM	Pathogenic	0.93	D
MutationAssessor	Uncertain	2.9	.;.;M
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.0	.;D;.
REVEL	Uncertain	0.62
Sift	Uncertain	0.022	.;D;.
Sift4G	Uncertain	0.034	D;D;D
Polyphen		0.95	.;.;P
Vest4		0.62
MutPred		0.13		.;.;Loss of methylation at K34 (P = 0.0681);
MVP		0.95
MPC		0.15
ClinPred		0.97	D
GERP RS		5.7
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		3.8
Varity_R		0.55
gMVP		0.084

Splicing

Name	Calibrated prediction	Score	Prediction
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

Publications

LitVar

Other links and lift over

dbSNP: rs377765758; hg19: chr8-92083386;