2-169895228-C-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_172070.4(UBR3):c.1153C>A(p.Leu385Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000288 in 1,388,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000029 ( 0 hom. )
Consequence
UBR3
NM_172070.4 missense
NM_172070.4 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 1.75
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27455765).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
UBR3 | NM_172070.4 | c.1153C>A | p.Leu385Ile | missense_variant | 7/39 | ENST00000272793.11 | NP_742067.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
UBR3 | ENST00000272793.11 | c.1153C>A | p.Leu385Ile | missense_variant | 7/39 | 5 | NM_172070.4 | ENSP00000272793 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000288 AC: 4AN: 1388230Hom.: 0 Cov.: 30 AF XY: 0.00000292 AC XY: 2AN XY: 684766
GnomAD4 exome
AF:
AC:
4
AN:
1388230
Hom.:
Cov.:
30
AF XY:
AC XY:
2
AN XY:
684766
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
AF:
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 | Apr 12, 2023 | The c.1153C>A (p.L385I) alteration is located in exon 7 (coding exon 7) of the UBR3 gene. This alteration results from a C to A substitution at nucleotide position 1153, causing the leucine (L) at amino acid position 385 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);
MVP
MPC
1.9
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at