rs11553473

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_003345.5(UBE2I):​c.73G>A​(p.Val25Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,674 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

UBE2I
NM_003345.5 missense

Scores

2
8
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.86
Variant links:
Genes affected
UBE2I (HGNC:12485): (ubiquitin conjugating enzyme E2 I) The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. Four alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1
In a site Interaction with RANBP2 (size 0) in uniprot entity UBC9_HUMAN
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
UBE2INM_003345.5 linkuse as main transcriptc.73G>A p.Val25Met missense_variant 3/7 ENST00000397514.8 NP_003336.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
UBE2IENST00000397514.8 linkuse as main transcriptc.73G>A p.Val25Met missense_variant 3/71 NM_003345.5 ENSP00000380649.3 P63279

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461674
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
727156
show subpopulations
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Uncertain
0.069
T
BayesDel_noAF
Benign
-0.14
CADD
Pathogenic
30
DANN
Uncertain
1.0
DEOGEN2
Benign
0.16
T;T;T;T;.;T;T;T;T;T
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.88
.;.;.;.;D;.;.;D;D;D
M_CAP
Benign
0.036
D
MetaRNN
Uncertain
0.57
D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.91
T
MutationAssessor
Uncertain
2.4
M;M;M;M;.;M;M;M;.;.
PrimateAI
Pathogenic
0.91
D
PROVEAN
Benign
-1.7
N;N;N;N;N;N;N;N;N;N
REVEL
Benign
0.18
Sift
Benign
0.044
D;D;D;D;D;D;D;D;T;D
Sift4G
Benign
0.19
T;T;T;T;T;T;T;T;T;T
Polyphen
0.99
D;D;D;D;.;D;D;D;.;D
Vest4
0.65
MutPred
0.44
Gain of ubiquitination at K30 (P = 0.0579);Gain of ubiquitination at K30 (P = 0.0579);Gain of ubiquitination at K30 (P = 0.0579);Gain of ubiquitination at K30 (P = 0.0579);Gain of ubiquitination at K30 (P = 0.0579);Gain of ubiquitination at K30 (P = 0.0579);Gain of ubiquitination at K30 (P = 0.0579);Gain of ubiquitination at K30 (P = 0.0579);Gain of ubiquitination at K30 (P = 0.0579);Gain of ubiquitination at K30 (P = 0.0579);
MVP
0.59
MPC
2.1
ClinPred
0.88
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.55
gMVP
0.95

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11553473; hg19: chr16-1364300; API