10-23439541-C-T

Variant names:

• chr10-23439541-C-T
• rs147006133
• NM_001145373.3:c.84C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BA1

The NM_001145373.3(OTUD1):​c.84C>T​(p.Ala28Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00845 in 1,380,678 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0086 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0084 (88 hom.)
• Consequence: OTUD1 NM_001145373.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.781

Genes affected

OTUD1 (HGNC:27346): (OTU deubiquitinase 1) Deubiquitinating enzymes (DUBs; see MIM 603478) are proteases that specifically cleave ubiquitin (MIM 191339) linkages, negating the action of ubiquitin ligases. DUBA7 belongs to a DUB subfamily characterized by an ovarian tumor (OTU) domain.[supplied by OMIM, May 2008]

ENSG00000287124 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 10-23439541-C-T is Benign according to our data. Variant chr10-23439541-C-T is described in ClinVar as [Benign]. Clinvar id is 3037482.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.781 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OTUD1	NM_001145373.3	c.84C>T	p.Ala28Ala	synonymous_variant	Exon 1 of 1	ENST00000376495.5	NP_001138845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OTUD1	ENST00000376495.5	c.84C>T	p.Ala28Ala	synonymous_variant	Exon 1 of 1	6	NM_001145373.3	ENSP00000365678.3
ENSG00000287124	ENST00000702412.1	n.88+496C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00863 AC: 1304 AN: 151026 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00414

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0213

Gnomad ASJ AF: 0.0258

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00644

Gnomad FIN AF: 0.000781

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.00880

Gnomad OTH AF: 0.0208

GnomAD3 exomes AF: 0.00957 AC: 471 AN: 49220 Hom.: 11 AF XY: 0.00899 AC XY: 262 AN XY: 29150

Gnomad AFR exome AF: 0.00836

Gnomad AMR exome AF: 0.00900

Gnomad ASJ exome AF: 0.0222

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00505

Gnomad FIN exome AF: 0.000869

Gnomad NFE exome AF: 0.0109

Gnomad OTH exome AF: 0.0209

GnomAD4 exome AF: 0.00843 AC: 10360 AN: 1229542 Hom.: 88 Cov.: 31 AF XY: 0.00851 AC XY: 5148 AN XY: 605038

Gnomad4 AFR exome AF: 0.00579

Gnomad4 AMR exome AF: 0.0113

Gnomad4 ASJ exome AF: 0.0227

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00525

Gnomad4 FIN exome AF: 0.00108

Gnomad4 NFE exome AF: 0.00843

Gnomad4 OTH exome AF: 0.0123

GnomAD4 genome AF: 0.00862 AC: 1303 AN: 151136 Hom.: 11 Cov.: 32 AF XY: 0.00842 AC XY: 622 AN XY: 73854

Gnomad4 AFR AF: 0.00413

Gnomad4 AMR AF: 0.0212

Gnomad4 ASJ AF: 0.0258

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00644

Gnomad4 FIN AF: 0.000781

Gnomad4 NFE AF: 0.00880

Gnomad4 OTH AF: 0.0206

Alfa AF: 0.00230 Hom.: 0

Bravo AF: 0.0105

Asia WGS AF: 0.00204 AC: 7 AN: 3442

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

OTUD1-related disorder Benign:1

Apr 12, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	7.1
DANN	Benign	0.94

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: rs147006133; hg19: chr10-23728470; COSMIC: COSV64713469;