Variant 15-31483800-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001382637.1(OTUD7A):c.2296C>T(p.Pro766Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000141 in 1,024,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 𝑓 0.00024 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

OTUD7A
NM_001382637.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.11

Variant links:

Genes affected

OTUD7A (HGNC:20718): (OTU deubiquitinase 7A) The protein encoded by this gene is a deubiquitinizing enzyme and possible tumor suppressor. The encoded protein acts on TNF receptor associated factor 6 (TRAF6) to control nuclear factor kappa B expression. However, this gene is downregulated by SNAIL1 in hepatocellular carcinoma cells, contributing to their progression and malignancy. [provided by RefSeq, Aug 2016]

OTUD7A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12957808).

BS2

High AC in GnomAd4 at 35 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTUD7A	NM_001382637.1 linkuse as main transcript	c.2296C>T	p.Pro766Ser	missense_variant	13/13	ENST00000307050.6	NP_001369566.1
OTUD7A	NM_130901.3 linkuse as main transcript	c.2275C>T	p.Pro759Ser	missense_variant	14/14		NP_570971.1	Q8TE49-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OTUD7A	ENST00000307050.6 linkuse as main transcript	c.2296C>T	p.Pro766Ser	missense_variant	13/13	1	NM_001382637.1	ENSP00000305926.5	Q8TE49-2
OTUD7A	ENST00000560598.2 linkuse as main transcript	c.2275C>T	p.Pro759Ser	missense_variant	14/14	5		ENSP00000453883.2	Q8TE49-1H0YN66
OTUD7A	ENST00000678495.1 linkuse as main transcript	c.2275C>T	p.Pro759Ser	missense_variant	11/11			ENSP00000503326.1	Q8TE49-1

Frequencies

GnomAD3 genomes

AF:

0.000234

AC:

AN:

145264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000617

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000272

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:

0.0000764

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000124

AC:

109

AN:

879080

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

AN XY:

409834

show subpopulations

Gnomad4 AFR exome

AF:

0.000536

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:

0.000121

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.000241

AC:

AN:

145374

Hom.:

Cov.:

AF XY:

0.000297

AC XY:

AN XY:

70714

show subpopulations

Gnomad4 AFR

AF:

0.000640

Gnomad4 AMR

AF:

0.000272

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000764

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000337

Hom.:

Bravo

AF:

0.000291

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

Aug 19, 2024

The c.2275C>T (p.P759S) alteration is located in exon 11 (coding exon 11) of the OTUD7A gene. This alteration results from a C to T substitution at nucleotide position 2275, causing the proline (P) at amino acid position 759 to be replaced by a serine (S). 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

0.070

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.023

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.47

M_CAP

Benign

0.080

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.73

REVEL

Benign

0.087

Sift

Uncertain

0.017

Sift4G

Benign

0.26

Polyphen

0.44

Vest4

0.15

MutPred

0.26

Gain of phosphorylation at P759 (P = 0.0058);

MVP

0.082

ClinPred

0.49

GERP RS

2.0

Varity_R

0.065

gMVP

0.40

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