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19-55401578-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_014501.3(UBE2S):c.527A>C(p.Glu176Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0738 in 1,606,250 control chromosomes in the GnomAD database, including 4,972 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.066 ( 407 hom., cov: 32)
Exomes 𝑓: 0.075 ( 4565 hom. )

Consequence

UBE2S
NM_014501.3 missense

Scores

1
17

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.38
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 -14 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0017818809).
BP6
Variant 19-55401578-T-G is Benign according to our data. Variant chr19-55401578-T-G is described in ClinVar as [Benign]. Clinvar id is 770812.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0846 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UBE2SNM_014501.3 linkuse as main transcriptc.527A>C p.Glu176Ala missense_variant 4/4 ENST00000264552.14
RPL28NM_001363697.1 linkuse as main transcriptc.325-1365T>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UBE2SENST00000264552.14 linkuse as main transcriptc.527A>C p.Glu176Ala missense_variant 4/41 NM_014501.3 P1
RPL28ENST00000560055.5 linkuse as main transcriptc.325-1365T>G intron_variant 3
UBE2SENST00000587845.5 linkuse as main transcript downstream_gene_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0665
AC:
10120
AN:
152082
Hom.:
407
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0321
Gnomad AMI
AF:
0.190
Gnomad AMR
AF:
0.0758
Gnomad ASJ
AF:
0.143
Gnomad EAS
AF:
0.00136
Gnomad SAS
AF:
0.0159
Gnomad FIN
AF:
0.0738
Gnomad MID
AF:
0.111
Gnomad NFE
AF:
0.0864
Gnomad OTH
AF:
0.0888
GnomAD3 exomes
AF:
0.0528
AC:
12341
AN:
233570
Hom.:
441
AF XY:
0.0516
AC XY:
6623
AN XY:
128386
show subpopulations
Gnomad AFR exome
AF:
0.0257
Gnomad AMR exome
AF:
0.0494
Gnomad ASJ exome
AF:
0.111
Gnomad EAS exome
AF:
0.000458
Gnomad SAS exome
AF:
0.0128
Gnomad FIN exome
AF:
0.0624
Gnomad NFE exome
AF:
0.0698
Gnomad OTH exome
AF:
0.0770
GnomAD4 exome
AF:
0.0745
AC:
108386
AN:
1454050
Hom.:
4565
Cov.:
30
AF XY:
0.0729
AC XY:
52702
AN XY:
723070
show subpopulations
Gnomad4 AFR exome
AF:
0.0302
Gnomad4 AMR exome
AF:
0.0549
Gnomad4 ASJ exome
AF:
0.129
Gnomad4 EAS exome
AF:
0.000454
Gnomad4 SAS exome
AF:
0.0149
Gnomad4 FIN exome
AF:
0.0710
Gnomad4 NFE exome
AF:
0.0827
Gnomad4 OTH exome
AF:
0.0757
GnomAD4 genome
AF:
0.0665
AC:
10119
AN:
152200
Hom.:
407
Cov.:
32
AF XY:
0.0645
AC XY:
4801
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.0320
Gnomad4 AMR
AF:
0.0757
Gnomad4 ASJ
AF:
0.143
Gnomad4 EAS
AF:
0.00136
Gnomad4 SAS
AF:
0.0162
Gnomad4 FIN
AF:
0.0738
Gnomad4 NFE
AF:
0.0864
Gnomad4 OTH
AF:
0.0879
Alfa
AF:
0.0792
Hom.:
159
Bravo
AF:
0.0675
TwinsUK
AF:
0.0777
AC:
288
ALSPAC
AF:
0.0797
AC:
307
ExAC
AF:
0.0488
AC:
5800

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.046
BayesDel_addAF
Benign
-0.62
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
7.1
DANN
Benign
0.55
DEOGEN2
Benign
0.023
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.0083
N
LIST_S2
Benign
0.12
T
MetaRNN
Benign
0.0018
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.20
N
MutationTaster
Benign
0.85
D;N
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-0.28
N
REVEL
Benign
0.086
Sift
Benign
0.94
T
Sift4G
Benign
0.73
T
Polyphen
0.0
B
Vest4
0.013
MPC
1.2
ClinPred
0.00054
T
GERP RS
0.76
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3
Varity_R
0.031
gMVP
0.30

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: rs61748180; hg19: chr19-55912946; COSMIC: COSV52740410; COSMIC: COSV52740410; API