15-31483600-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001382637.1(OTUD7A):c.2496G>A(p.Ser832=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00154 in 1,223,872 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0078 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00067 (5 hom.)
• Consequence: OTUD7A NM_001382637.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.858

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 15-31483600-C-T is Benign according to our data. Variant chr15-31483600-C-T is described in ClinVar as [Benign]. Clinvar id is 3033632.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.858 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00783 (1166/148890) while in subpopulation AFR AF= 0.0272 (1121/41168). AF 95% confidence interval is 0.0259. There are 11 homozygotes in gnomad4. There are 522 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1168 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTUD7A	NM_001382637.1	c.2496G>A	p.Ser832=	synonymous_variant	13/13	ENST00000307050.6
OTUD7A	NM_130901.3	c.2475G>A	p.Ser825=	synonymous_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTUD7A	ENST00000307050.6	c.2496G>A	p.Ser832=	synonymous_variant	13/13	1	NM_001382637.1	P2
OTUD7A	ENST00000560598.2	c.2475G>A	p.Ser825=	synonymous_variant	14/14	5		A2
OTUD7A	ENST00000678495.1	c.2475G>A	p.Ser825=	synonymous_variant	11/11			A2

Frequencies

GnomAD3 genomes AF: 0.00785 AC: 1168 AN: 148788 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0274

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00233

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: 0.0000300

Gnomad OTH AF: 0.00390

GnomAD3 exomes AF: 0.000403 AC: 1 AN: 2484 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 1708

Gnomad AFR exome AF: 0.0714

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000671 AC: 721 AN: 1074982 Hom.: 5 Cov.: 28 AF XY: 0.000580 AC XY: 300 AN XY: 516996

Gnomad4 AFR exome AF: 0.0296

Gnomad4 AMR exome AF: 0.00208

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000372

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000653

Gnomad4 OTH exome AF: 0.00163

GnomAD4 genome AF: 0.00783 AC: 1166 AN: 148890 Hom.: 11 Cov.: 32 AF XY: 0.00718 AC XY: 522 AN XY: 72662

Gnomad4 AFR AF: 0.0272

Gnomad4 AMR AF: 0.00233

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000300

Gnomad4 OTH AF: 0.00386

Alfa AF: 0.00140 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

OTUD7A-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 12, 2019

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	-0.52
Cadd	Benign	8.6
Dann	Benign	0.94

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: rs78774681; hg19: chr15-31775803;