3-23499711-T-C

Variant names:

• chr3-23499711-T-C
• NM_152653.4:c.331T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152653.4(UBE2E2):​c.331T>C​(p.Ser111Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBE2E2 NM_152653.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.74
• Publications: 0 publications found

Genes affected

UBE2E2 (HGNC:12478): (ubiquitin conjugating enzyme E2 E2) Enables ISG15 transferase activity and ubiquitin conjugating enzyme activity. Involved in protein modification by small protein conjugation. Acts upstream of or within cellular response to DNA damage stimulus and positive regulation of G1/S transition of mitotic cell cycle. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13440225).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152653.4. 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
	UBE2E2	NM_152653.4	MANE Select	c.331T>C	p.Ser111Pro	missense	Exon 4 of 6	NP_689866.1	Q96LR5
	UBE2E2	NM_001370225.1		c.331T>C	p.Ser111Pro	missense	Exon 4 of 6	NP_001357154.1	Q96LR5
	UBE2E2	NM_001370226.1		c.331T>C	p.Ser111Pro	missense	Exon 4 of 6	NP_001357155.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2E2	ENST00000396703.6	TSL:1 MANE Select	c.331T>C	p.Ser111Pro	missense	Exon 4 of 6	ENSP00000379931.1	Q96LR5
	UBE2E2	ENST00000335798.8	TSL:1	n.228-32843T>C		intron	N/A	ENSP00000338340.4	F8W8F0
	UBE2E2	ENST00000425792.5	TSL:2	c.331T>C	p.Ser111Pro	missense	Exon 4 of 6	ENSP00000401053.1	Q96LR5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

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	Uncertain	0.54
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Benign	0.41
DEOGEN2	Benign	0.064	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	-2.2	N
PhyloP100		3.7
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.23
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0010	B
Vest4		0.56
MutPred		0.54		Gain of catalytic residue at S111 (P = 0.0265)
MVP		0.23
MPC		1.3
ClinPred		0.52	D
GERP RS		5.7
PromoterAI		0.0049	Neutral
Varity_R		0.78
gMVP		0.90
Mutation Taster		=81/19	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

hg19: chr3-23541202;