NM_003347.4:c.202A>G

Variant names:

• chr22-21610935-A-G
• NM_003347.4:c.202A>G

Variant summary

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

The NM_003347.4(UBE2L3):​c.202A>G​(p.Ile68Val) variant causes a missense change involving the alteration of a conserved nucleotide. 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: UBE2L3 NM_003347.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.21
• Publications: 0 publications found

Genes affected

UBE2L3 (HGNC:12488): (ubiquitin conjugating enzyme E2 L3) The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s). This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. This enzyme is demonstrated to participate in the ubiquitination of p53, c-Fos, and the NF-kB precursor p105 in vitro. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2009]

UBE2L3 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

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=0.23615092).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003347.4. 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
	UBE2L3	NM_003347.4	MANE Select	c.202A>G	p.Ile68Val	missense	Exon 3 of 4	NP_003338.1	P68036-1
	UBE2L3	NM_001256355.1		c.376A>G	p.Ile126Val	missense	Exon 3 of 4	NP_001243284.1	P68036-3
	UBE2L3	NM_001256356.2		c.106A>G	p.Ile36Val	missense	Exon 2 of 3	NP_001243285.1	P68036-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2L3	ENST00000342192.9	TSL:1 MANE Select	c.202A>G	p.Ile68Val	missense	Exon 3 of 4	ENSP00000344259.5	P68036-1
	UBE2L3	ENST00000458578.6	TSL:2	c.376A>G	p.Ile126Val	missense	Exon 3 of 4	ENSP00000400906.2	P68036-3
	UBE2L3	ENST00000920161.1		c.202A>G	p.Ile68Val	missense	Exon 3 of 5	ENSP00000590220.1

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	Benign	0.18
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.085
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0050	N
PhyloP100		9.2
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.20
Sift	Benign	0.47	T
Sift4G	Benign	0.89	T
Polyphen		0.0	B
Vest4		0.41
MutPred		0.54		Loss of sheet (P = 0.0817)
MVP		0.87
MPC		1.7
ClinPred		0.71	D
GERP RS		5.4
Varity_R		0.13
gMVP		0.62
Mutation Taster		=57/43	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: chr22-21965224;