Variant X-70062846-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_207320.3(OTUD6A):c.322C>G(p.Arg108Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000335 in 1,193,734 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

OTUD6A
NM_207320.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0780

Variant links:

Genes affected

OTUD6A (HGNC:32312): (OTU deubiquitinase 6A) Deubiquitinating enzymes (DUBs; see MIM 603478) are proteases that specifically cleave ubiquitin (MIM 191339) linkages, negating the action of ubiquitin ligases. DUBA2 belongs to a DUB subfamily characterized by an ovarian tumor (OTU) domain.[supplied by OMIM, May 2008]

OTUD6A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.15930635).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTUD6A	NM_207320.3 linkuse as main transcript	c.322C>G	p.Arg108Gly	missense_variant	1/1	ENST00000338352.3	NP_997203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTUD6A	ENST00000338352.3 linkuse as main transcript	c.322C>G	p.Arg108Gly	missense_variant	1/1		NM_207320.3	ENSP00000339389	P1

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111944

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34118

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000664

AC:

AN:

150505

Hom.:

AF XY:

0.00

AC XY:

AN XY:

46621

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000157

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000185

AC:

AN:

1081790

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

352428

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:

0.00000240

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111944

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34118

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000151

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

Dec 27, 2023

The c.322C>G (p.R108G) alteration is located in exon 1 (coding exon 1) of the OTUD6A gene. This alteration results from a C to G substitution at nucleotide position 322, causing the arginine (R) at amino acid position 108 to be replaced by a glycine (G). 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

0.13

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.22

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.34

M_CAP

Benign

0.049

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.88

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Pathogenic

-5.3

REVEL

Benign

0.11

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.0070

Polyphen

0.98

Vest4

0.096

MutPred

0.34

Loss of stability (P = 0.0563);

MVP

0.31

MPC

1.6

ClinPred

0.89

GERP RS

-1.8

Varity_R

0.32

gMVP

0.92

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