15-31573615-A-G

Variant names:

• chr15-31573615-A-G
• rs10519728
• NM_001382637.1:c.152-3418T>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.152-3418T>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 152,204 control chromosomes in the GnomAD database, including 29,707 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 (29707 hom., cov: 34)
• Consequence: OTUD7A NM_001382637.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTUD7A	NM_001382637.1	c.152-3418T>C		intron_variant	Intron 3 of 12	ENST00000307050.6	NP_001369566.1
OTUD7A	NM_130901.3	c.152-3418T>C		intron_variant	Intron 4 of 13		NP_570971.1
OTUD7A	NM_001329907.2	c.152-3418T>C		intron_variant	Intron 4 of 10		NP_001316836.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTUD7A	ENST00000307050.6	c.152-3418T>C		intron_variant	Intron 3 of 12	1	NM_001382637.1	ENSP00000305926.5

Frequencies

GnomAD3 genomes AF: 0.601 AC: 91335 AN: 152086 Hom.: 29641 Cov.: 34

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.722

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: 91461 AN: 152204 Hom.: 29707 Cov.: 34 AF XY: 0.598 AC XY: 44478 AN XY: 74424

African (AFR) AF: 0.836 AC: 34723 AN: 41544

American (AMR) AF: 0.603 AC: 9214 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1772 AN: 3472

East Asian (EAS) AF: 0.914 AC: 4744 AN: 5190

South Asian (SAS) AF: 0.427 AC: 2062 AN: 4826

European-Finnish (FIN) AF: 0.450 AC: 4769 AN: 10590

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

European-Non Finnish (NFE) AF: 0.473 AC: 32166 AN: 67978

Other (OTH) AF: 0.581 AC: 1225 AN: 2110

Alfa AF: 0.560 Hom.: 3872

Bravo AF: 0.631

Asia WGS AF: 0.668 AC: 2324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.92
DANN	Benign	0.56
PhyloP100		-1.6
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: rs10519728; hg19: chr15-31865818;