Variant 2-169872252-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_172070.4(UBR3):c.562C>A(p.Gln188Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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: 3.60

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13278678).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBR3	NM_172070.4 linkuse as main transcript	c.562C>A	p.Gln188Lys	missense_variant	2/39	ENST00000272793.11	NP_742067.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBR3	ENST00000272793.11 linkuse as main transcript	c.562C>A	p.Gln188Lys	missense_variant	2/39	5	NM_172070.4	ENSP00000272793.5		Q6ZT12-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1370928

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

674928

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 09, 2024

The c.562C>A (p.Q188K) alteration is located in exon 2 (coding exon 2) of the UBR3 gene. This alteration results from a C to A substitution at nucleotide position 562, causing the glutamine (Q) at amino acid position 188 to be replaced by a lysine (K). 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

0.085

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.14

T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

0.085

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.80

.;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

0.75

N;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.54

N;N

REVEL

Benign

0.28

Sift

Benign

0.57

T;T

Sift4G

Benign

0.97

T;T

Polyphen

0.071

B;B

Vest4

0.20

MutPred

0.42

Gain of catalytic residue at Q188 (P = 0.0047);Gain of catalytic residue at Q188 (P = 0.0047);

MVP

0.043

MPC

1.0

ClinPred

0.38

GERP RS

5.6

Varity_R

0.18

gMVP

0.27

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over