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GeneBe

19-55401545-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014501.3(UBE2S):c.560G>T(p.Gly187Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000892 in 1,458,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G187D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

UBE2S
NM_014501.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.164
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.051785856).
BS2
High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UBE2SNM_014501.3 linkuse as main transcriptc.560G>T p.Gly187Val missense_variant 4/4 ENST00000264552.14
RPL28NM_001363697.1 linkuse as main transcriptc.325-1398C>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UBE2SENST00000264552.14 linkuse as main transcriptc.560G>T p.Gly187Val missense_variant 4/41 NM_014501.3 P1
RPL28ENST00000560055.5 linkuse as main transcriptc.325-1398C>A intron_variant 3
UBE2SENST00000587845.5 linkuse as main transcript downstream_gene_variant 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000165
AC:
4
AN:
241798
Hom.:
0
AF XY:
0.0000151
AC XY:
2
AN XY:
132632
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000583
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:
0.0000185
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000892
AC:
13
AN:
1458154
Hom.:
0
Cov.:
29
AF XY:
0.00000827
AC XY:
6
AN XY:
725426
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000449
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:
0.00000720
Gnomad4 OTH exome
AF:
0.0000499
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756
ExAC
AF:
0.0000168
AC:
2

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.560G>T (p.G187V) 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 560, causing the glycine (G) at amino acid position 187 to be replaced by a valine (V). 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
0.069
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
3.0
DANN
Benign
0.76
DEOGEN2
Benign
0.040
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.59
T
M_CAP
Benign
0.046
D
MetaRNN
Benign
0.052
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.81
L
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-0.92
N
REVEL
Benign
0.011
Sift
Benign
0.13
T
Sift4G
Benign
0.16
T
Polyphen
0.085
B
Vest4
0.079
MutPred
0.29
Loss of glycosylation at P188 (P = 0.2196);
MVP
0.30
MPC
1.5
ClinPred
0.032
T
GERP RS
-1.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.9
Varity_R
0.053
gMVP
0.29

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: rs762051776; hg19: chr19-55912913; API