15-31571757-A-G

Variant names:

• chr15-31571757-A-G
• rs3903373
• NM_001382637.1:c.152-1560T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382637.1(OTUD7A):​c.152-1560T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 152,090 control chromosomes in the GnomAD database, including 29,691 homozygotes. 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: 𝑓 0.60 (29691 hom., cov: 32)
• Consequence: OTUD7A NM_001382637.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.475
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

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.152-1560T>C		intron	N/A	NP_001369566.1
	OTUD7A	NM_130901.3		c.152-1560T>C		intron	N/A	NP_570971.1
	OTUD7A	NM_001329907.2		c.152-1560T>C		intron	N/A	NP_001316836.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD7A	ENST00000307050.6	TSL:1 MANE Select	c.152-1560T>C		intron	N/A	ENSP00000305926.5
	OTUD7A	ENST00000558371.5	TSL:1	n.446-1560T>C		intron	N/A
	OTUD7A	ENST00000560598.2	TSL:5	c.152-1560T>C		intron	N/A	ENSP00000453883.2

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91268 AN: 151972 Hom.: 29625 Cov.: 32

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.914

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.473

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.601 AC: 91394 AN: 152090 Hom.: 29691 Cov.: 32 AF XY: 0.598 AC XY: 44427 AN XY: 74340

African (AFR) AF: 0.836 AC: 34695 AN: 41510

American (AMR) AF: 0.602 AC: 9207 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1770 AN: 3470

East Asian (EAS) AF: 0.914 AC: 4733 AN: 5180

South Asian (SAS) AF: 0.428 AC: 2058 AN: 4814

European-Finnish (FIN) AF: 0.450 AC: 4754 AN: 10560

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.473 AC: 32163 AN: 67956

Other (OTH) AF: 0.581 AC: 1227 AN: 2112

Alfa AF: 0.521 Hom.: 28233

Bravo AF: 0.631

Asia WGS AF: 0.668 AC: 2324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.5
DANN	Benign	0.24
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

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: rs3903373; hg19: chr15-31863960;