rs10519680

Variant names:

• chr15-31738494-C-T
• rs10519680
• NM_001382637.1:c.-99-81417G>A

Variant summary

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

The NM_001382637.1(OTUD7A):​c.-99-81417G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 152,198 control chromosomes in the GnomAD database, including 129 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 0.030 (129 hom., cov: 32)
• Consequence: OTUD7A NM_001382637.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 1 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.064 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTUD7A	NM_001382637.1	c.-99-81417G>A		intron_variant	Intron 1 of 12	ENST00000307050.6	NP_001369566.1
OTUD7A	NM_130901.3	c.-222-49013G>A		intron_variant	Intron 1 of 13		NP_570971.1
OTUD7A	NM_001329907.2	c.-222-49013G>A		intron_variant	Intron 1 of 10		NP_001316836.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTUD7A	ENST00000307050.6	c.-99-81417G>A		intron_variant	Intron 1 of 12	1	NM_001382637.1	ENSP00000305926.5
OTUD7A	ENST00000558371.5	n.73-49013G>A		intron_variant	Intron 1 of 5	1
OTUD7A	ENST00000560598.2	c.-222-49013G>A		intron_variant	Intron 1 of 13	5		ENSP00000453883.2
OTUD7A	ENST00000560536.5	n.-222-49013G>A		intron_variant	Intron 2 of 8	2		ENSP00000453622.1

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 4607 AN: 152080 Hom.: 128 Cov.: 32

Gnomad AFR AF: 0.0661

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0216

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.0114

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0184

Gnomad OTH AF: 0.0296

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

GnomAD4 genome AF: 0.0303 AC: 4614 AN: 152198 Hom.: 129 Cov.: 32 AF XY: 0.0290 AC XY: 2156 AN XY: 74402

African (AFR) AF: 0.0661 AC: 2743 AN: 41514

American (AMR) AF: 0.0216 AC: 330 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0254 AC: 88 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00291 AC: 14 AN: 4818

European-Finnish (FIN) AF: 0.0114 AC: 121 AN: 10606

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0184 AC: 1253 AN: 68004

Other (OTH) AF: 0.0293 AC: 62 AN: 2114

Alfa AF: 0.0233 Hom.: 11

Bravo AF: 0.0329

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.45
DANN	Benign	0.73
PhyloP100		-0.027

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10519680; hg19: chr15-32030697;