Genetic Variant UBR3:p.Lys295Asn (chr2-169877534-G-C) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_172070.4(UBR3):c.885G>C(p.Lys295Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000718 in 1,391,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000072 ( 0 hom. )

Consequence

UBR3
NM_172070.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.10

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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.27619356).

BS2

High AC in GnomAdExome4 at 10 AD gene.

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.885G>C	p.Lys295Asn	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.885G>C	p.Lys295Asn	missense	Exon 4 of 39	ENSP00000272793.5	Q6ZT12-1
UBR3	ENST00000949146.1		c.885G>C	p.Lys295Asn	missense	Exon 4 of 40	ENSP00000619205.1
UBR3	ENST00000949147.1		c.885G>C	p.Lys295Asn	missense	Exon 4 of 39	ENSP00000619206.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000668

AC:

AN:

149700

AF XY:

0.0000126

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000169

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000718

AC:

AN:

1391930

Hom.:

Cov.:

AF XY:

0.00000583

AC XY:

AN XY:

686342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31060

American (AMR)

AF:

0.00

AC:

AN:

32936

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24998

East Asian (EAS)

AF:

0.00

AC:

AN:

35596

South Asian (SAS)

AF:

0.00

AC:

AN:

77198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49302

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5672

European-Non Finnish (NFE)

AF:

0.00000928

AC:

AN:

1077412

Other (OTH)

AF:

0.00

AC:

AN:

57756

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Pathogenic

0.77

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.073

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.022

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.1

PhyloP100

3.1

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.94

REVEL

Benign

0.18

Sift

Benign

0.26

Sift4G

Benign

0.26

Polyphen

1.0

Vest4

0.39

MutPred

0.49

Gain of ubiquitination at K291 (P = 0.0232)

MVP

0.17

MPC

2.0

ClinPred

0.44

GERP RS

2.6

Varity_R

0.15

gMVP

0.49

Mutation Taster

=63/37

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over