15-31483468-C-CGCGTCG

Position:

• chr15-31483468-C-CGCGTCG

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4 BS2

The NM_001382637.1(OTUD7A):​c.2622_2627dupCGACGC​(p.Ala876_Pro877insAspAla) variant causes a disruptive inframe insertion change. The variant allele was found at a frequency of 0.0000073 in 1,233,678 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000073 (0 hom.)
• Consequence: OTUD7A NM_001382637.1 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.33

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_benign. Variant got -2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001382637.1.
• BS2: High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTUD7A	NM_001382637.1	c.2622_2627dupCGACGC	p.Ala876_Pro877insAspAla	disruptive_inframe_insertion	13/13	ENST00000307050.6	NP_001369566.1
OTUD7A	NM_130901.3	c.2601_2606dupCGACGC	p.Ala869_Pro870insAspAla	disruptive_inframe_insertion	14/14		NP_570971.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTUD7A	ENST00000307050.6	c.2622_2627dupCGACGC	p.Ala876_Pro877insAspAla	disruptive_inframe_insertion	13/13	1	NM_001382637.1	ENSP00000305926.5
OTUD7A	ENST00000560598.2	c.2601_2606dupCGACGC	p.Ala869_Pro870insAspAla	disruptive_inframe_insertion	14/14	5		ENSP00000453883.2
OTUD7A	ENST00000678495.1	c.2601_2606dupCGACGC	p.Ala869_Pro870insAspAla	disruptive_inframe_insertion	11/11			ENSP00000503326.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000730 AC: 9 AN: 1233678 Hom.: 0 Cov.: 29 AF XY: 0.00000658 AC XY: 4 AN XY: 607772

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000155

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000799

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Apr 26, 2022

Gene of Uncertain Significance -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs748063208; hg19: chr15-31775671;