3-23499711-T-C

Position:

• chr3-23499711-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2E2	NM_152653.4	c.331T>C	p.Ser111Pro	missense_variant	4/6	ENST00000396703.6	NP_689866.1
UBE2E2	NM_001370225.1	c.331T>C	p.Ser111Pro	missense_variant	4/6		NP_001357154.1
UBE2E2	NM_001370226.1	c.331T>C	p.Ser111Pro	missense_variant	4/6		NP_001357155.1
UBE2E2	XM_047448843.1	c.331T>C	p.Ser111Pro	missense_variant	4/6		XP_047304799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2E2	ENST00000396703.6	c.331T>C	p.Ser111Pro	missense_variant	4/6	1	NM_152653.4	ENSP00000379931.1
UBE2E2	ENST00000335798.8	n.228-32843T>C		intron_variant		1		ENSP00000338340.4
UBE2E2	ENST00000425792.5	c.331T>C	p.Ser111Pro	missense_variant	4/6	2		ENSP00000401053.1
UBE2E2	ENST00000452894.5	c.403T>C	p.Ser135Pro	missense_variant	5/6	3		ENSP00000392800.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2024

The c.331T>C (p.S111P) alteration is located in exon 4 (coding exon 3) of the UBE2E2 gene. This alteration results from a T to C substitution at nucleotide position 331, causing the serine (S) at amino acid position 111 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;.;T;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	.;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	-2.2	N;.;N;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.5	N;N;N;.
REVEL	Benign	0.23
Sift	Benign	1.0	T;T;T;.
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0010	B;.;B;.
Vest4		0.56
MutPred		0.54		Gain of catalytic residue at S111 (P = 0.0265);.;Gain of catalytic residue at S111 (P = 0.0265);.;
MVP		0.23
MPC		1.3
ClinPred		0.52	D
GERP RS		5.7
Varity_R		0.78
gMVP		0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-23541202;