8-91071167-C-T

Variant names:

• chr8-91071167-C-T
• NM_016023.5:c.112C>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016023.5(OTUD6B):​c.112C>T​(p.Pro38Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000253 in 1,461,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: OTUD6B NM_016023.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.29

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.77

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTUD6B	NM_016023.5	c.112C>T	p.Pro38Ser	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.112C>T	p.Pro38Ser	missense_variant	Exon 2 of 7	1	NM_016023.5	ENSP00000384190.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000253 AC: 37 AN: 1461200 Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17 AN XY: 726920

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: 0.0000306

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome Cov.: 32

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.075	T;T;T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D;.;D
M_CAP	Pathogenic	0.29	D
MetaRNN	Pathogenic	0.77	D;D;D
MetaSVM	Pathogenic	0.93	D
MutationAssessor	Uncertain	2.5	.;.;M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-5.0	.;D;.
REVEL	Pathogenic	0.65
Sift	Uncertain	0.024	.;D;.
Sift4G	Benign	0.22	T;T;T
Polyphen		0.99	.;.;D
Vest4		0.71
MutPred		0.23		.;.;Gain of phosphorylation at P38 (P = 0.0213);
MVP		0.97
MPC		0.15
ClinPred		0.98	D
GERP RS		5.7
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.7
Varity_R		0.37
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-92083395;