rs6493688

Positions:

• chr15-31480672-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382637.1(OTUD7A):​c.*2622C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,260 control chromosomes in the GnomAD database, including 6,346 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 0.28 (6346 hom., cov: 34)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: OTUD7A NM_001382637.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OTUD7A	NM_001382637.1	c.*2622C>T		3_prime_UTR_variant	13/13	ENST00000307050.6	NP_001369566.1
OTUD7A	NM_130901.3	c.*2622C>T		3_prime_UTR_variant	14/14		NP_570971.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OTUD7A	ENST00000307050	c.*2622C>T		3_prime_UTR_variant	13/13	1	NM_001382637.1	ENSP00000305926.5

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43063 AN: 152130 Hom.: 6341 Cov.: 34

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.295

GnomAD4 exome AF: 0.250 AC: 3 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.333 AC XY: 2 AN XY: 6

Gnomad4 SAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.283 AC: 43084 AN: 152248 Hom.: 6346 Cov.: 34 AF XY: 0.282 AC XY: 20953 AN XY: 74424

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.297

Alfa AF: 0.312 Hom.: 12155

Bravo AF: 0.292

Asia WGS AF: 0.316 AC: 1097 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs6493688; hg19: chr15-31772875;