rs17401847

Variant names:

• chr1-19911973-A-G
• rs17401847
• NM_015207.2:c.*4227A>G

Variant summary

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

The NM_015207.2(OTUD3):​c.*4227A>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 0.124 in 152,364 control chromosomes in the GnomAD database, including 1,333 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 0.12 (1333 hom., cov: 32)
  • Exomes 𝑓: 0.11 (0 hom.)
• Consequence: OTUD3 NM_015207.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTUD3	NM_015207.2	c.*4227A>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.*4227A>G		3_prime_UTR_variant	Exon 8 of 8	1	NM_015207.2	ENSP00000364261.3

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18834 AN: 152098 Hom.: 1330 Cov.: 32

Gnomad AFR AF: 0.0753

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0855

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.119

GnomAD4 exome AF: 0.110 AC: 16 AN: 146 Hom.: 0 Cov.: 0 AF XY: 0.110 AC XY: 9 AN XY: 82

Gnomad4 EAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.124 AC: 18863 AN: 152218 Hom.: 1333 Cov.: 32 AF XY: 0.129 AC XY: 9574 AN XY: 74414

Gnomad4 AFR AF: 0.0754

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.0856

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.118

Alfa AF: 0.133 Hom.: 1347

Bravo AF: 0.118

Asia WGS AF: 0.117 AC: 406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.45

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: rs17401847; hg19: chr1-20238466;