Variant 15-31483646-C-A 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_001382637.1(OTUD7A):c.2450G>T(p.Ser817Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000256 in 1,173,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)

Exomes 𝑓: 9.7e-7 ( 0 hom. )

Consequence

OTUD7A
NM_001382637.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.25

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 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=0.21932486).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTUD7A	NM_001382637.1 linkuse as main transcript	c.2450G>T	p.Ser817Ile	missense_variant	13/13	ENST00000307050.6
OTUD7A	NM_130901.3 linkuse as main transcript	c.2429G>T	p.Ser810Ile	missense_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTUD7A	ENST00000307050.6 linkuse as main transcript	c.2450G>T	p.Ser817Ile	missense_variant	13/13	1	NM_001382637.1	P2	Q8TE49-2
OTUD7A	ENST00000560598.2 linkuse as main transcript	c.2429G>T	p.Ser810Ile	missense_variant	14/14	5		A2	Q8TE49-1
OTUD7A	ENST00000678495.1 linkuse as main transcript	c.2429G>T	p.Ser810Ile	missense_variant	11/11			A2	Q8TE49-1

Frequencies

GnomAD3 genomes

AF:

0.0000135

AC:

AN:

147884

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000134

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:

9.75e-7

AC:

AN:

1026078

Hom.:

Cov.:

AF XY:

0.00000206

AC XY:

AN XY:

486230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000159

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000135

AC:

AN:

147884

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

72066

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000134

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:

0.0000264

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

Jul 13, 2022

The c.2429G>T (p.S810I) alteration is located in exon 11 (coding exon 11) of the OTUD7A gene. This alteration results from a G to T substitution at nucleotide position 2429, causing the serine (S) at amino acid position 810 to be replaced by an isoleucine (I). 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

Uncertain

0.53

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

Cadd

Uncertain

Dann

Benign

0.95

DEOGEN2

Benign

0.040

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.81

M_CAP

Pathogenic

0.45

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

MutationTaster

Benign

0.94

D;D

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-1.6

REVEL

Benign

0.19

Sift

Benign

0.47

Sift4G

Benign

0.082

Polyphen

0.23

Vest4

0.46

MutPred

0.26

Loss of glycosylation at S810 (P = 0.0217);

MVP

0.22

ClinPred

0.59

GERP RS

2.7

Varity_R

0.17

gMVP

0.72

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