rs16956801

Variant names:

• chr15-31500388-C-A
• rs16956801
• NM_001382637.1:c.1171+1302G>T

Variant summary

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

The NM_001382637.1(OTUD7A):​c.1171+1302G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,318 control chromosomes in the GnomAD database, including 1,560 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 0.14 (1560 hom., cov: 33)
• Consequence: OTUD7A NM_001382637.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.713
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.191 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.1171+1302G>T		intron	N/A	NP_001369566.1
	OTUD7A	NM_130901.3		c.1150+1302G>T		intron	N/A	NP_570971.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD7A	ENST00000307050.6	TSL:1 MANE Select	c.1171+1302G>T		intron	N/A	ENSP00000305926.5
	OTUD7A	ENST00000560598.2	TSL:5	c.1150+1302G>T		intron	N/A	ENSP00000453883.2
	OTUD7A	ENST00000678495.1		c.1150+1302G>T		intron	N/A	ENSP00000503326.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21382 AN: 152200 Hom.: 1555 Cov.: 33

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.0595

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.141 AC: 21420 AN: 152318 Hom.: 1560 Cov.: 33 AF XY: 0.138 AC XY: 10317 AN XY: 74492

African (AFR) AF: 0.135 AC: 5621 AN: 41556

American (AMR) AF: 0.197 AC: 3018 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 431 AN: 3470

East Asian (EAS) AF: 0.126 AC: 655 AN: 5190

South Asian (SAS) AF: 0.0597 AC: 288 AN: 4822

European-Finnish (FIN) AF: 0.109 AC: 1157 AN: 10628

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9751 AN: 68022

Other (OTH) AF: 0.156 AC: 330 AN: 2112

Alfa AF: 0.143 Hom.: 870

Bravo AF: 0.147

Asia WGS AF: 0.0970 AC: 339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.27
DANN	Benign	0.59
PhyloP100		-0.71
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: rs16956801; hg19: chr15-31792591;