OTUD7A p.Leu378Leu

Variant names:

• chr15-31501726-C-C
• NM_001382637.1:c.

Your query was ambiguous. Multiple possible variants found:

• chr15-31501727--
• chr15-31501727-A-G
• chr15-31501727-A-T
• chr15-31501727-A-C
• chr15-31501727-AAG-TAA
• chr15-31501727-AAG-CAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001382637.1(OTUD7A):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.		exon_region	Exon 10 of 13	NP_001369566.1	Q8TE49-2
	OTUD7A	NM_130901.3		c.		exon_region	Exon 11 of 14	NP_570971.1	Q8TE49-1
	OTUD7A	NM_001329907.2		c.		exon_region	Exon 11 of 11	NP_001316836.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD7A	ENST00000307050.6	TSL:1 MANE Select	c.		exon_region	Exon 10 of 13	ENSP00000305926.5	Q8TE49-2
	OTUD7A	ENST00000926297.1		c.		exon_region	Exon 11 of 14	ENSP00000596356.1
	OTUD7A	ENST00000926298.1		c.		exon_region	Exon 10 of 13	ENSP00000596357.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.4

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: chr15-31793929;