rs12124726

Positions:

• chr1-19882976-A-C

Variant summary

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

The NM_015207.2(OTUD3):​c.221+242A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,098 control chromosomes in the GnomAD database, including 9,167 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 0.34 (9167 hom., cov: 33)
• Consequence: OTUD3 NM_015207.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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]

LOC105376823 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTUD3	NM_015207.2	c.221+242A>C		intron_variant		ENST00000375120.4
LOC105376823	XR_947028.3	n.41+6148T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTUD3	ENST00000375120.4	c.221+242A>C		intron_variant		1	NM_015207.2	P1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51856 AN: 151978 Hom.: 9160 Cov.: 33

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.337

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.341 AC: 51902 AN: 152098 Hom.: 9167 Cov.: 33 AF XY: 0.338 AC XY: 25120 AN XY: 74348

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.335

Alfa AF: 0.376 Hom.: 5990

Bravo AF: 0.335

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs12124726; hg19: chr1-20209469;