rs3738122

Variant names:

• chr1-19912367-C-G
• rs3738122
• NM_015207.2:c.*4621C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
OTUD3	NM_015207.2	c.*4621C>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000375120.4	NP_056022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTUD3	ENST00000375120.4	c.*4621C>G		3_prime_UTR_variant	Exon 8 of 8	1	NM_015207.2	ENSP00000364261.3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.234 AC: 29 AN: 124

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.184 AC: 14 AN: 76

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.283 AC: 13 AN: 46

Other (OTH) AF: 0.00 AC: 0 AN: 6

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

African (AFR) AF: 0.0895 AC: 3721 AN: 41568

American (AMR) AF: 0.174 AC: 2655 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 849 AN: 3470

East Asian (EAS) AF: 0.0633 AC: 328 AN: 5180

South Asian (SAS) AF: 0.0821 AC: 396 AN: 4824

European-Finnish (FIN) AF: 0.225 AC: 2386 AN: 10598

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18907 AN: 67972

Other (OTH) AF: 0.209 AC: 441 AN: 2114

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
PhyloP100		-0.85
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: rs3738122; hg19: chr1-20238860;