UBE2S p.Gly52Arg

Variant names:

• chr19-55404476-C-G
• NM_014501.3:c.154G>C
• UBE2S p.Gly52Arg

Your query was ambiguous. Multiple possible variants found:

• chr19-55404476-C-G
• chr19-55404476-C-T
• chr19-55404474-CCC-ACG
• chr19-55404474-CCC-GCG
• chr19-55404474-CCC-TCG
• chr19-55404474-CCC-TCT

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014501.3(UBE2S):​c.154G>C​(p.Gly52Arg) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 13/22 in silico tools predict a damaging outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G52W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: UBE2S NM_014501.3 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.14
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.888

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.154G>C	p.Gly52Arg	missense splice_region	Exon 3 of 4	NP_055316.2	Q16763

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2S	ENST00000264552.14	TSL:1 MANE Select	c.154G>C	p.Gly52Arg	missense splice_region	Exon 3 of 4	ENSP00000264552.8	Q16763
	UBE2S	ENST00000917162.1		c.367G>C	p.Gly123Arg	missense splice_region	Exon 4 of 5	ENSP00000587221.1
	UBE2S	ENST00000587845.5	TSL:2	c.154G>C	p.Gly52Arg	missense splice_region	Exon 3 of 5	ENSP00000467409.1	K7EPJ1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.26	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.90
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Pathogenic	0.29	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	0.70	D
MutationAssessor	Pathogenic	3.9	H
PhyloP100		7.1
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-7.5	D
REVEL	Pathogenic	0.82
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.91
gMVP		0.90
Mutation Taster		=23/77	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-55915844;