Genetic Variant UBR3:p.Pro83Leu (chr2-169827755-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_172070.4(UBR3):c.248C>T(p.Pro83Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UBR3
NM_172070.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.399

Publications

0 publications found

Variant links:

Genes affected

UBR3 (HGNC:30467): (ubiquitin protein ligase E3 component n-recognin 3) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in several processes, including cellular protein metabolic process; sensory perception of smell; and suckling behavior. Predicted to act upstream of or within in utero embryonic development and olfactory behavior. Predicted to be integral component of membrane. Predicted to be part of ubiquitin ligase complex. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

UBR3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12321022).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172070.4. 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
	UBR3	NM_172070.4	MANE Select	c.248C>T	p.Pro83Leu	missense	Exon 1 of 39	NP_742067.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBR3	ENST00000272793.11	TSL:5 MANE Select	c.248C>T	p.Pro83Leu	missense	Exon 1 of 39	ENSP00000272793.5	Q6ZT12-1
UBR3	ENST00000949146.1		c.248C>T	p.Pro83Leu	missense	Exon 1 of 40	ENSP00000619205.1
UBR3	ENST00000949147.1		c.248C>T	p.Pro83Leu	missense	Exon 1 of 39	ENSP00000619206.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1132778

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

543636

African (AFR)

AF:

0.00

AC:

AN:

24472

American (AMR)

AF:

0.00

AC:

AN:

13370

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16256

East Asian (EAS)

AF:

0.00

AC:

AN:

27040

South Asian (SAS)

AF:

0.00

AC:

AN:

31176

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3590

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

946546

Other (OTH)

AF:

0.00

AC:

AN:

45872

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.070

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.060

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.66

M_CAP

Benign

0.080

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.40

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.2

REVEL

Benign

0.042

Sift

Uncertain

0.0060

Sift4G

Pathogenic

0.0

Polyphen

0.47

Vest4

0.20

MutPred

0.24

Loss of glycosylation at P83 (P = 0.0355)

MVP

0.043

MPC

0.79

ClinPred

0.65

GERP RS

2.9

PromoterAI

-0.062

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.16

gMVP

0.37

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over