Variant 15-31483512-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001382637.1(OTUD7A):c.2584T>C(p.Phe862Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000717 in 1,395,386 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

OTUD7A
NM_001382637.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.86

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 -4 ACMG points.

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTUD7A	NM_001382637.1 linkuse as main transcript	c.2584T>C	p.Phe862Leu	missense_variant	13/13	ENST00000307050.6
OTUD7A	NM_130901.3 linkuse as main transcript	c.2563T>C	p.Phe855Leu	missense_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTUD7A	ENST00000307050.6 linkuse as main transcript	c.2584T>C	p.Phe862Leu	missense_variant	13/13	1	NM_001382637.1	P2	Q8TE49-2
OTUD7A	ENST00000560598.2 linkuse as main transcript	c.2563T>C	p.Phe855Leu	missense_variant	14/14	5		A2	Q8TE49-1
OTUD7A	ENST00000678495.1 linkuse as main transcript	c.2563T>C	p.Phe855Leu	missense_variant	11/11			A2	Q8TE49-1

Frequencies

GnomAD3 genomes

AF:

0.0000135

AC:

AN:

148636

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000488

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000562

AC:

AN:

1246646

Hom.:

Cov.:

AF XY:

0.00000651

AC XY:

AN XY:

614718

show subpopulations

Gnomad4 AFR exome

AF:

0.000248

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:

9.94e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000202

AC:

AN:

148740

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72532

show subpopulations

Gnomad4 AFR

AF:

0.0000730

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Jun 12, 2023

The c.2563T>C (p.F855L) alteration is located in exon 11 (coding exon 11) of the OTUD7A gene. This alteration results from a T to C substitution at nucleotide position 2563, causing the phenylalanine (F) at amino acid position 855 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

AlphaMissense

Pathogenic

0.90

BayesDel_addAF

Benign

-0.077

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.57

M_CAP

Pathogenic

0.46

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.0

MutationTaster

Benign

0.99

D;D

PrimateAI

Pathogenic

0.97

PROVEAN

Benign

-0.65

REVEL

Benign

0.20

Sift

Benign

0.21

Sift4G

Benign

0.58

Polyphen

0.96

Vest4

0.49

MutPred

0.35

Gain of disorder (P = 0.1344);

MVP

0.43

ClinPred

0.95

GERP RS

3.8

Varity_R

0.27

gMVP

0.35

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