15-31483801-C-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001382637.1(OTUD7A):c.2295G>C(p.Val765=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 1,024,014 control chromosomes in the GnomAD database, including 247,930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (42596 hom., cov: 28)
  • Exomes 𝑓: 0.68 (205334 hom.)
• Consequence: OTUD7A NM_001382637.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.869

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 15-31483801-C-G is Benign according to our data. Variant chr15-31483801-C-G is described in ClinVar as [Benign]. Clinvar id is 1227617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.869 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTUD7A	NM_001382637.1	c.2295G>C	p.Val765=	synonymous_variant	13/13	ENST00000307050.6
OTUD7A	NM_130901.3	c.2274G>C	p.Val758=	synonymous_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTUD7A	ENST00000307050.6	c.2295G>C	p.Val765=	synonymous_variant	13/13	1	NM_001382637.1	P2
OTUD7A	ENST00000560598.2	c.2274G>C	p.Val758=	synonymous_variant	14/14	5		A2
OTUD7A	ENST00000678495.1	c.2274G>C	p.Val758=	synonymous_variant	11/11			A2

Frequencies

GnomAD3 genomes AF: 0.756 AC: 109881 AN: 145254 Hom.: 42549 Cov.: 28

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.711

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.753

GnomAD3 exomes AF: 0.687 AC: 184 AN: 268 Hom.: 64 AF XY: 0.682 AC XY: 101 AN XY: 148

Gnomad NFE exome AF: 0.683

Gnomad OTH exome AF: 0.833

GnomAD4 exome AF: 0.682 AC: 599108 AN: 878658 Hom.: 205334 Cov.: 40 AF XY: 0.681 AC XY: 278710 AN XY: 409532

Gnomad4 AFR exome AF: 0.933

Gnomad4 AMR exome AF: 0.760

Gnomad4 ASJ exome AF: 0.698

Gnomad4 EAS exome AF: 0.916

Gnomad4 SAS exome AF: 0.580

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.676

Gnomad4 OTH exome AF: 0.699

GnomAD4 genome AF: 0.757 AC: 109977 AN: 145356 Hom.: 42596 Cov.: 28 AF XY: 0.752 AC XY: 53190 AN XY: 70702

Gnomad4 AFR AF: 0.916

Gnomad4 AMR AF: 0.756

Gnomad4 ASJ AF: 0.698

Gnomad4 EAS AF: 0.922

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.630

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.754

Alfa AF: 0.711 Hom.: 4789

Bravo AF: 0.782

Asia WGS AF: 0.730 AC: 1793 AN: 2456

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 02, 2018

- -

OTUD7A-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 06, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.86
Dann	Benign	0.52

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

Other links and lift over

dbSNP: rs2338682; hg19: chr15-31776004; COSMIC: COSV61035977;