chr15-31501727-A-C

Variant names:

• chr15-31501727-A-C
• rs7164569
• NM_001382637.1:c.1134T>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001382637.1(OTUD7A):​c.1134T>G​(p.Leu378Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: -1.41
• Publications: 19 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP7: Synonymous conserved (PhyloP=-1.41 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD7A	NM_001382637.1	MANE Select	c.1134T>G	p.Leu378Leu	synonymous	Exon 10 of 13	NP_001369566.1
	OTUD7A	NM_130901.3		c.1113T>G	p.Leu371Leu	synonymous	Exon 11 of 14	NP_570971.1
	OTUD7A	NM_001329907.2		c.1134T>G	p.Leu378Leu	synonymous	Exon 11 of 11	NP_001316836.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD7A	ENST00000307050.6	TSL:1 MANE Select	c.1134T>G	p.Leu378Leu	synonymous	Exon 10 of 13	ENSP00000305926.5
	OTUD7A	ENST00000560598.2	TSL:5	c.1113T>G	p.Leu371Leu	synonymous	Exon 11 of 14	ENSP00000453883.2
	OTUD7A	ENST00000678495.1		c.1113T>G	p.Leu371Leu	synonymous	Exon 8 of 11	ENSP00000503326.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251424 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.73
DANN	Benign	0.61
PhyloP100		-1.4

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

Other links and lift over

dbSNP: rs7164569; hg19: chr15-31793930;