1-19907706-A-C

Position:

• chr1-19907706-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015207.2(OTUD3):​c.1157A>C​(p.Gln386Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OTUD3 NM_015207.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.05

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OTUD3	NM_015207.2	c.1157A>C	p.Gln386Pro	missense_variant	8/8	ENST00000375120.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OTUD3	ENST00000375120.4	c.1157A>C	p.Gln386Pro	missense_variant	8/8	1	NM_015207.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.1157A>C (p.Q386P) alteration is located in exon 8 (coding exon 8) of the OTUD3 gene. This alteration results from a A to C substitution at nucleotide position 1157, causing the glutamine (Q) at amino acid position 386 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0054	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.50	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.10
Sift	Uncertain	0.016	D
Sift4G	Benign	0.11	T
Polyphen		0.61	P
Vest4		0.62
MutPred		0.30		Gain of loop (P = 0.0166);
MVP		0.51
MPC		1.0
ClinPred		0.87	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-20234199;