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GeneBe

19-55401633-C-T

Variant summary

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

The NM_014501.3(UBE2S):c.472G>A(p.Ala158Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000399 in 1,605,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

UBE2S
NM_014501.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.48
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0500578).
BS2
High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UBE2SNM_014501.3 linkuse as main transcriptc.472G>A p.Ala158Thr missense_variant 4/4 ENST00000264552.14
RPL28NM_001363697.1 linkuse as main transcriptc.325-1310C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UBE2SENST00000264552.14 linkuse as main transcriptc.472G>A p.Ala158Thr missense_variant 4/41 NM_014501.3 P1
UBE2SENST00000587845.5 linkuse as main transcriptc.559G>A p.Ala187Thr missense_variant 5/52
RPL28ENST00000560055.5 linkuse as main transcriptc.325-1310C>T intron_variant 3

Frequencies

GnomAD3 genomes
AF:
0.000171
AC:
26
AN:
152180
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000627
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000540
AC:
12
AN:
222190
Hom.:
0
AF XY:
0.0000407
AC XY:
5
AN XY:
122908
show subpopulations
Gnomad AFR exome
AF:
0.000480
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000602
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000412
Gnomad OTH exome
AF:
0.000183
GnomAD4 exome
AF:
0.0000261
AC:
38
AN:
1453514
Hom.:
0
Cov.:
30
AF XY:
0.0000180
AC XY:
13
AN XY:
722770
show subpopulations
Gnomad4 AFR exome
AF:
0.000629
Gnomad4 AMR exome
AF:
0.0000690
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000721
Gnomad4 OTH exome
AF:
0.0000501
GnomAD4 genome
AF:
0.000171
AC:
26
AN:
152298
Hom.:
0
Cov.:
32
AF XY:
0.000188
AC XY:
14
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.000625
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000848
Hom.:
0
Bravo
AF:
0.000181
ExAC
AF:
0.0000847
AC:
10

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 GeneticsDec 14, 2023The c.472G>A (p.A158T) alteration is located in exon 4 (coding exon 4) of the UBE2S gene. This alteration results from a G to A substitution at nucleotide position 472, causing the alanine (A) at amino acid position 158 to be replaced by a threonine (T). 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
0.076
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
15
DANN
Benign
0.97
DEOGEN2
Benign
0.035
T;.
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.46
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.78
T;T
M_CAP
Uncertain
0.14
D
MetaRNN
Benign
0.050
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.69
N;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-1.0
N;.
REVEL
Benign
0.039
Sift
Benign
0.42
T;.
Sift4G
Benign
0.35
T;.
Polyphen
0.21
B;.
Vest4
0.17
MutPred
0.24
Gain of glycosylation at A158 (P = 0.0065);.;
MVP
0.66
MPC
1.1
ClinPred
0.034
T
GERP RS
4.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.11
gMVP
0.35

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: rs556845857; hg19: chr19-55913001; API