15-31501727-AAG-CAA

Variant names:

• chr15-31501727-AAG-CAA
• NM_001382637.1:c.1132_1134delCTTinsTTG
• OTUD7A p.379

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001382637.1(OTUD7A):​c.1132_1134delCTTinsTTG​(p.379) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OTUD7A NM_001382637.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.35
• Publications: 0 publications found

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]

OTUD7A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382637.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD7A	NM_001382637.1	MANE Select	c.1132_1134delCTTinsTTG	p.379	synonymous	N/A	NP_001369566.1	Q8TE49-2
	OTUD7A	NM_130901.3		c.1111_1113delCTTinsTTG	p.372	synonymous	N/A	NP_570971.1	Q8TE49-1
	OTUD7A	NM_001329907.2		c.1132_1134delCTTinsTTG	p.379	synonymous	N/A	NP_001316836.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD7A	ENST00000307050.6	TSL:1 MANE Select	c.1132_1134delCTTinsTTG	p.379	synonymous	N/A	ENSP00000305926.5	Q8TE49-2
	OTUD7A	ENST00000926297.1		c.1132_1134delCTTinsTTG	p.379	synonymous	N/A	ENSP00000596356.1
	OTUD7A	ENST00000926298.1		c.1132_1134delCTTinsTTG	p.379	synonymous	N/A	ENSP00000596357.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.4

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr15-31793930;