rs3738122

Positions:

• chr1-19912367-C-G

Variant summary

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

The NM_015207.2(OTUD3):​c.*4621C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,470 control chromosomes in the GnomAD database, including 3,534 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 0.20 (3526 hom., cov: 32)
  • Exomes 𝑓: 0.22 (8 hom.)
• Consequence: OTUD3 NM_015207.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.855

Genes affected

OTUD3 (HGNC:29038): (OTU deubiquitinase 3) Enables thiol-dependent deubiquitinase. Acts upstream of or within negative regulation of protein kinase B signaling; protein deubiquitination; and protein stabilization. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTUD3	NM_015207.2	c.*4621C>G		3_prime_UTR_variant	8/8	ENST00000375120.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTUD3	ENST00000375120.4	c.*4621C>G		3_prime_UTR_variant	8/8	1	NM_015207.2	P1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30043 AN: 152100 Hom.: 3524 Cov.: 32

Gnomad AFR AF: 0.0897

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.245

Gnomad EAS AF: 0.0630

Gnomad SAS AF: 0.0806

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.222 AC: 56 AN: 252 Hom.: 8 Cov.: 0 AF XY: 0.201 AC XY: 29 AN XY: 144

Gnomad4 EAS exome AF: 0.234

Gnomad4 FIN exome AF: 0.184

Gnomad4 NFE exome AF: 0.283

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.197 AC: 30050 AN: 152218 Hom.: 3526 Cov.: 32 AF XY: 0.191 AC XY: 14214 AN XY: 74408

Gnomad4 AFR AF: 0.0895

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.245

Gnomad4 EAS AF: 0.0633

Gnomad4 SAS AF: 0.0821

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.278

Gnomad4 OTH AF: 0.209

Alfa AF: 0.246 Hom.: 692

Bravo AF: 0.189

Asia WGS AF: 0.0600 AC: 209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.25
DANN	Benign	0.64

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: rs3738122; hg19: chr1-20238860;