rs762051776

Variant names:

• chr19-55401545-C-A
• rs762051776
• NM_014501.3:c.560G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-55401545-C-A
• chr19-55401545-C-G
• chr19-55401545-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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. 16/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.164
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014501.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2S	NM_014501.3	MANE Select	c.560G>T	p.Gly187Val	missense	Exon 4 of 4	NP_055316.2	Q16763
	RPL28	NM_001363697.1		c.325-1398C>A		intron	N/A	NP_001350626.1	H0YKD8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2S	ENST00000264552.14	TSL:1 MANE Select	c.560G>T	p.Gly187Val	missense	Exon 4 of 4	ENSP00000264552.8	Q16763
	UBE2S	ENST00000917162.1		c.773G>T	p.Gly258Val	missense	Exon 5 of 5	ENSP00000587221.1
	RPL28	ENST00000560055.5	TSL:3	c.325-1398C>A		intron	N/A	ENSP00000452763.1	H0YKD8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000165 AC: 4 AN: 241798 AF XY: 0.0000151

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 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

African (AFR) AF: 0.00 AC: 0 AN: 33332

American (AMR) AF: 0.0000449 AC: 2 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52214

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4292

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111612

Other (OTH) AF: 0.0000499 AC: 3 AN: 60176

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000168 AC: 2

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.16
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
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs762051776; hg19: chr19-55912913;