15-31483861-C-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001382637.1(OTUD7A):c.2235G>T(p.Ala745=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000311 in 986,008 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00031 (3 hom.)
• Consequence: OTUD7A NM_001382637.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.04

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 15-31483861-C-A is Benign according to our data. Variant chr15-31483861-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2645113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.04 with no splicing effect.
• BS2: High AC in GnomAd at 46 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTUD7A	NM_001382637.1	c.2235G>T	p.Ala745=	synonymous_variant	13/13	ENST00000307050.6
OTUD7A	NM_130901.3	c.2214G>T	p.Ala738=	synonymous_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTUD7A	ENST00000307050.6	c.2235G>T	p.Ala745=	synonymous_variant	13/13	1	NM_001382637.1	P2
OTUD7A	ENST00000560598.2	c.2214G>T	p.Ala738=	synonymous_variant	14/14	5		A2
OTUD7A	ENST00000678495.1	c.2214G>T	p.Ala738=	synonymous_variant	11/11			A2

Frequencies

GnomAD3 genomes AF: 0.000316 AC: 46 AN: 145388 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000204

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000400

Gnomad SAS AF: 0.00584

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000183

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000311 AC: 261 AN: 840518 Hom.: 3 Cov.: 46 AF XY: 0.000332 AC XY: 129 AN XY: 389024

Gnomad4 AFR exome AF: 0.000252

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00647

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000146

Gnomad4 OTH exome AF: 0.000938

GnomAD4 genome AF: 0.000316 AC: 46 AN: 145490 Hom.: 0 Cov.: 29 AF XY: 0.000367 AC XY: 26 AN XY: 70798

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000204

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000401

Gnomad4 SAS AF: 0.00584

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000183

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000162

ClinVar

Significance: Benign/Likely 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

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

OTUD7A: BS1, BS2 -

OTUD7A-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 12, 2019

This variant is classified as likely 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	-0.76
Cadd	Benign	4.9
Dann	Benign	0.81

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: rs867747505; hg19: chr15-31776064;