19-55401578-T-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

UBE2S links:

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]

RPL28 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
UBE2S	NM_014501.3 link	c.527A>C	p.Glu176Ala	missense_variant	Exon 4 of 4	ENST00000264552.14	NP_055316.2	Q16763
RPL28	NM_001363697.1 link	c.325-1365T>G		intron_variant	Intron 4 of 4		NP_001350626.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UBE2S	ENST00000264552.14 link	c.527A>C	p.Glu176Ala	missense_variant	Exon 4 of 4	1	NM_014501.3	ENSP00000264552.8	Q16763
RPL28	ENST00000560055.5 link	c.325-1365T>G		intron_variant	Intron 4 of 4	3		ENSP00000452763.1	H0YKD8
UBE2S	ENST00000587845.5 link	c.*1A>C		downstream_gene_variant		2		ENSP00000467409.1	K7EPJ1
UBE2S	ENST00000589978.1 link	c.*210A>C		downstream_gene_variant		5		ENSP00000466388.1	K7EM75

Frequencies

GnomAD3 genomes

AF:

0.0665

AC:

10120

AN:

152082

Hom.:

407

Cov.:

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.:

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.:

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.046

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.60

CADD

Benign

7.1

DANN

Benign

0.55

DEOGEN2

Benign

0.023

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0083

LIST_S2

Benign

0.12

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.20

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.28

REVEL

Benign

0.086

Sift

Benign

0.94

Sift4G

Benign

0.73

Polyphen

0.0

Vest4

0.013

MPC

1.2

ClinPred

0.00054

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over