Variant 1-149944297-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020205.4(OTUD7B):c.2092A>G(p.Ile698Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

OTUD7B
NM_020205.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

Variant links:

Genes affected

OTUD7B (HGNC:16683): (OTU deubiquitinase 7B) Enables Lys48-specific deubiquitinase activity and thiol-dependent deubiquitinase. Involved in several processes, including negative regulation of I-kappaB kinase/NF-kappaB signaling; negative regulation of macromolecule metabolic process; and protein deubiquitination. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

OTUD7B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06625962).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTUD7B	NM_020205.4 linkuse as main transcript	c.2092A>G	p.Ile698Val	missense_variant	12/12	ENST00000581312.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTUD7B	ENST00000581312.6 linkuse as main transcript	c.2092A>G	p.Ile698Val	missense_variant	12/12	1	NM_020205.4	P1	Q6GQQ9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246252

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133584

show subpopulations

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:

0.0000331

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458738

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725432

show subpopulations

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:

9.01e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2023

The c.2092A>G (p.I698V) alteration is located in exon 12 (coding exon 11) of the OTUD7B gene. This alteration results from a A to G substitution at nucleotide position 2092, causing the isoleucine (I) at amino acid position 698 to be replaced by a valine (V). 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

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.033

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.32

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.61

M_CAP

Benign

0.0045

MetaRNN

Benign

0.066

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.90

PrimateAI

Benign

0.42

Sift4G

Benign

0.65

Polyphen

0.0

Vest4

0.074

MutPred

0.25

Gain of catalytic residue at I698 (P = 0.0687);

MVP

0.27

ClinPred

0.091

GERP RS

2.1

Varity_R

0.033

gMVP

0.14

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over