rs6493688

Variant names:

• chr15-31480672-G-A
• rs6493688
• NM_001382637.1:c.*2622C>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.*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
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD7A	NM_001382637.1	MANE Select	c.*2622C>T		3_prime_UTR	Exon 13 of 13	NP_001369566.1	Q8TE49-2
	OTUD7A	NM_130901.3		c.*2622C>T		3_prime_UTR	Exon 14 of 14	NP_570971.1	Q8TE49-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD7A	ENST00000307050.6	TSL:1 MANE Select	c.*2622C>T		3_prime_UTR	Exon 13 of 13	ENSP00000305926.5	Q8TE49-2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.125 AC: 1 AN: 8

Other (OTH) AF: 0.500 AC: 1 AN: 2

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

African (AFR) AF: 0.208 AC: 8656 AN: 41548

American (AMR) AF: 0.326 AC: 4984 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1320 AN: 3468

East Asian (EAS) AF: 0.371 AC: 1922 AN: 5180

South Asian (SAS) AF: 0.205 AC: 989 AN: 4828

European-Finnish (FIN) AF: 0.267 AC: 2829 AN: 10588

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21403 AN: 68014

Other (OTH) AF: 0.297 AC: 629 AN: 2116

Alfa AF: 0.307 Hom.: 20435

Bravo AF: 0.292

Asia WGS AF: 0.316 AC: 1097 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.56
PhyloP100		0.26

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: rs6493688; hg19: chr15-31772875;