15-31483730-T-TCGTCCCGCGCGCCC

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_001382637.1(OTUD7A):c.2365_2366insGGGCGCGCGGGACG(p.Glu789GlyfsTer203) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: OTUD7A NM_001382637.1 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.60

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 Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.718 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTUD7A	NM_001382637.1	c.2365_2366insGGGCGCGCGGGACG	p.Glu789GlyfsTer203	frameshift_variant	13/13	ENST00000307050.6
OTUD7A	NM_130901.3	c.2344_2345insGGGCGCGCGGGACG	p.Glu782GlyfsTer203	frameshift_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTUD7A	ENST00000307050.6	c.2365_2366insGGGCGCGCGGGACG	p.Glu789GlyfsTer203	frameshift_variant	13/13	1	NM_001382637.1	P2
OTUD7A	ENST00000560598.2	c.2344_2345insGGGCGCGCGGGACG	p.Glu782GlyfsTer203	frameshift_variant	14/14	5		A2
OTUD7A	ENST00000678495.1	c.2344_2345insGGGCGCGCGGGACG	p.Glu782GlyfsTer203	frameshift_variant	11/11			A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

OTUD7A-related disorder Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 30, 2023

The OTUD7A c.2331_2344dup14 variant is predicted to result in a frameshift and premature protein termination (p.Glu782Glyfs*203). which is predicted to result in an extension of the normal reading frame (p.Glu782Glyfs*203). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-31775933;