chr1-19911973-A-G

Variant names:

• chr1-19911973-A-G
• rs17401847
• NM_015207.2:c.*4227A>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.*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
• Publications: 5 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=-0.85).
• 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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.109 AC: 15 AN: 138

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.0754 AC: 3131 AN: 41534

American (AMR) AF: 0.159 AC: 2439 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 541 AN: 3466

East Asian (EAS) AF: 0.0856 AC: 443 AN: 5178

South Asian (SAS) AF: 0.145 AC: 696 AN: 4816

European-Finnish (FIN) AF: 0.192 AC: 2037 AN: 10600

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9233 AN: 68008

Other (OTH) AF: 0.118 AC: 250 AN: 2114

Alfa AF: 0.132 Hom.: 1738

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
PhyloP100		0.29
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: rs17401847; hg19: chr1-20238466;