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GeneBe

19-55401660-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_014501.3(UBE2S):c.445C>A(p.Arg149Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

UBE2S
NM_014501.3 missense

Scores

6
11
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.40
Variant links:
Genes affected
UBE2S (HGNC:17895): (ubiquitin conjugating enzyme E2 S) This gene encodes a member of the ubiquitin-conjugating enzyme family. The encoded protein is able to form a thiol ester linkage with ubiquitin in a ubiquitin activating enzyme-dependent manner, a characteristic property of ubiquitin carrier proteins. [provided by RefSeq, Jul 2008]
RPL28 (HGNC:10330): (ribosomal protein L28) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L28E family of ribosomal proteins. It is located in the cytoplasm. Variable expression of this gene in colorectal cancers compared to adjacent normal tissues has been observed, although no correlation between the level of expression and the severity of the disease has been found. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Oct 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.836

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UBE2SNM_014501.3 linkuse as main transcriptc.445C>A p.Arg149Ser missense_variant 4/4 ENST00000264552.14
RPL28NM_001363697.1 linkuse as main transcriptc.325-1283G>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UBE2SENST00000264552.14 linkuse as main transcriptc.445C>A p.Arg149Ser missense_variant 4/41 NM_014501.3 P1
UBE2SENST00000587845.5 linkuse as main transcriptc.532C>A p.Arg178Ser missense_variant 5/52
RPL28ENST00000560055.5 linkuse as main transcriptc.325-1283G>T intron_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1458240
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
725398
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.:
32

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 submitterclinical testingAmbry GeneticsJul 05, 2023The c.445C>A (p.R149S) alteration is located in exon 4 (coding exon 4) of the UBE2S gene. This alteration results from a C to A substitution at nucleotide position 445, causing the arginine (R) at amino acid position 149 to be replaced by a serine (S). 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
Pathogenic
0.65
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.030
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T;.
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Pathogenic
0.42
D
MetaRNN
Pathogenic
0.84
D;D
MetaSVM
Uncertain
0.10
D
MutationAssessor
Uncertain
2.3
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.87
D
PROVEAN
Uncertain
-3.7
D;.
REVEL
Pathogenic
0.69
Sift
Uncertain
0.0030
D;.
Sift4G
Uncertain
0.010
D;.
Polyphen
0.91
P;.
Vest4
0.54
MutPred
0.71
Gain of glycosylation at R149 (P = 0.0323);.;
MVP
0.83
MPC
1.4
ClinPred
0.98
D
GERP RS
3.5
Varity_R
0.82
gMVP
0.78

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.

Other links and lift over

hg19: chr19-55913028; API