8-91070332-C-T

Position:

• chr8-91070332-C-T

Variant summary

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

The ENST00000285420.8(OTUD6B):​c.38C>T​(p.Pro13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,460,952 control chromosomes in the GnomAD database, with no homozygous occurrence. 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: OTUD6B ENST00000285420.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.20

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:):

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=0.072230905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTUD6B	NM_016023.5	c.-53C>T		upstream_gene_variant		ENST00000404789.8	NP_057107.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTUD6B	ENST00000404789.8	c.-53C>T		upstream_gene_variant		1	NM_016023.5	ENSP00000384190.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000192 AC: 28 AN: 1460952 Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14 AN XY: 726676

Gnomad4 AFR exome AF: 0.0000299

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: 0.0000225

Gnomad4 OTH exome AF: 0.0000332

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

The c.38C>T (p.P13L) alteration is located in exon 1 (coding exon 1) of the OTUD6B gene. This alteration results from a C to T substitution at nucleotide position 38, causing the proline (P) at amino acid position 13 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.95
DANN	Benign	0.78
DEOGEN2	Benign	0.0060	T;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.46	T;.
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.072	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.010	.;N
REVEL	Benign	0.027
Sift	Benign	0.14	.;T
Vest4		0.097
MutPred		0.36		Loss of loop (P = 0.0112);Loss of loop (P = 0.0112);
MVP		0.23
MPC		0.018
ClinPred		0.19	T
GERP RS		0.83
gMVP		0.027

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: chr8-92082560; COSMIC: COSV53443927; COSMIC: COSV53443927;