rs12124726

Variant names:

• chr1-19882976-A-C
• rs12124726
• NM_015207.2:c.221+242A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 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]

LOC105376823 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015207.2. 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
	OTUD3	NM_015207.2	MANE Select	c.221+242A>C		intron	N/A	NP_056022.1	Q5T2D3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OTUD3	ENST00000375120.4	TSL:1 MANE Select	c.221+242A>C		intron	N/A	ENSP00000364261.3	Q5T2D3
	OTUD3	ENST00000916791.1		c.221+242A>C		intron	N/A	ENSP00000586850.1
	OTUD3	ENST00000880254.1		c.221+242A>C		intron	N/A	ENSP00000550313.1

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

African (AFR) AF: 0.267 AC: 11072 AN: 41512

American (AMR) AF: 0.330 AC: 5043 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1140 AN: 3462

East Asian (EAS) AF: 0.191 AC: 991 AN: 5176

South Asian (SAS) AF: 0.238 AC: 1149 AN: 4826

European-Finnish (FIN) AF: 0.405 AC: 4278 AN: 10566

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27094 AN: 67950

Other (OTH) AF: 0.335 AC: 708 AN: 2112

Alfa AF: 0.371 Hom.: 8260

Bravo AF: 0.335

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.3
DANN	Benign	0.82
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12124726; hg19: chr1-20209469;