Genetic Variant UBR3:p.Leu305Phe (chr2-169877562-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_172070.4(UBR3):c.913C>T(p.Leu305Phe) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L305V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UBR3
NM_172070.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.95

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2809404).

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.913C>T	p.Leu305Phe	missense	Exon 4 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.913C>T	p.Leu305Phe	missense	Exon 4 of 39	ENSP00000272793.5	Q6ZT12-1
UBR3	ENST00000949146.1		c.913C>T	p.Leu305Phe	missense	Exon 4 of 40	ENSP00000619205.1
UBR3	ENST00000949147.1		c.913C>T	p.Leu305Phe	missense	Exon 4 of 39	ENSP00000619206.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

154622

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1397148

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

689028

African (AFR)

AF:

0.00

AC:

AN:

31458

American (AMR)

AF:

0.00

AC:

AN:

34940

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25138

East Asian (EAS)

AF:

0.00

AC:

AN:

35634

South Asian (SAS)

AF:

0.00

AC:

AN:

78578

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49298

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078498

Other (OTH)

AF:

0.00

AC:

AN:

57914

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.084

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.015

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.1

PhyloP100

2.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.2

REVEL

Benign

0.17

Sift

Benign

0.054

Sift4G

Uncertain

0.057

Polyphen

1.0

Vest4

0.41

MutPred

0.35

Gain of sheet (P = 0.1208)

MVP

0.17

MPC

1.9

ClinPred

0.86

GERP RS

4.5

Varity_R

0.11

gMVP

0.37

Mutation Taster

=77/23

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

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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