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GeneBe

19-55401453-C-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_014501.3(UBE2S):c.652G>T(p.Ala218Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000735 in 1,605,286 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000078 ( 0 hom. )

Consequence

UBE2S
NM_014501.3 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.92
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 Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.2695623).
BS2
High AC in GnomAdExome4 at 114 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UBE2SNM_014501.3 linkuse as main transcriptc.652G>T p.Ala218Ser missense_variant 4/4 ENST00000264552.14
RPL28NM_001363697.1 linkuse as main transcriptc.325-1490C>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UBE2SENST00000264552.14 linkuse as main transcriptc.652G>T p.Ala218Ser missense_variant 4/41 NM_014501.3 P1
RPL28ENST00000560055.5 linkuse as main transcriptc.325-1490C>A intron_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152128
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000440
AC:
10
AN:
227416
Hom.:
0
AF XY:
0.0000476
AC XY:
6
AN XY:
126140
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000872
Gnomad OTH exome
AF:
0.000178
GnomAD4 exome
AF:
0.0000784
AC:
114
AN:
1453158
Hom.:
0
Cov.:
29
AF XY:
0.0000691
AC XY:
50
AN XY:
723166
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:
0.0000208
Gnomad4 NFE exome
AF:
0.0000945
Gnomad4 OTH exome
AF:
0.000133
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152128
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000683
AC:
8

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 GeneticsJun 03, 2022The c.652G>T (p.A218S) alteration is located in exon 4 (coding exon 4) of the UBE2S gene. This alteration results from a G to T substitution at nucleotide position 652, causing the alanine (A) at amino acid position 218 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
Benign
0.21
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.032
T
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.058
D
MetaRNN
Benign
0.27
T
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
0.97
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-0.44
N
REVEL
Benign
0.17
Sift
Benign
0.44
T
Sift4G
Benign
0.71
T
Polyphen
0.99
D
Vest4
0.34
MutPred
0.26
Gain of phosphorylation at A218 (P = 6e-04);
MVP
0.62
MPC
1.0
ClinPred
0.26
T
GERP RS
4.6
Varity_R
0.12
gMVP
0.36

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: rs749653893; hg19: chr19-55912821; API