Variant 17-76396413-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_022066.4(UBE2O):c.2524G>A(p.Val842Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

UBE2O
NM_022066.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.64

Variant links:

Genes affected

UBE2O (HGNC:29554): (ubiquitin conjugating enzyme E2 O) Enables ubiquitin conjugating enzyme activity and ubiquitin protein ligase activity. Involved in positive regulation of BMP signaling pathway; protein ubiquitination; and retrograde transport, endosome to Golgi. Located in cytoplasm and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

UBE2O links:

UBE2O (HGNC:):

UBE2O links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1830709).

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2O	NM_022066.4 linkuse as main transcript	c.2524G>A	p.Val842Met	missense_variant	14/18	ENST00000319380.12	NP_071349.3	Q9C0C9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UBE2O	ENST00000319380.12 linkuse as main transcript	c.2524G>A	p.Val842Met	missense_variant	14/18	1	NM_022066.4	ENSP00000323687.6	Q9C0C9
UBE2O	ENST00000587127.1 linkuse as main transcript	c.1066G>A	p.Val356Met	missense_variant	6/10	1		ENSP00000468498.1	K7ES11
UBE2O	ENST00000586409.5 linkuse as main transcript	n.2524G>A		non_coding_transcript_exon_variant	14/14	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251466

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 01, 2024

The c.2524G>A (p.V842M) alteration is located in exon 14 (coding exon 14) of the UBE2O gene. This alteration results from a G to A substitution at nucleotide position 2524, causing the valine (V) at amino acid position 842 to be replaced by a methionine (M). 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

0.13

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

Eigen

Benign

0.064

Eigen_PC

Benign

0.072

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.78

M_CAP

Benign

0.019

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.33

MutationAssessor

Benign

0.69

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.79

REVEL

Benign

0.19

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.054

Polyphen

0.98

Vest4

0.19

MutPred

0.073

Gain of glycosylation at P840 (P = 0.0879);

MVP

0.33

MPC

0.79

ClinPred

0.18

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.046

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over