NM_003347.4:c.311-2485C>T

Variant names:

• chr22-21619030-C-T
• rs4821116
• NM_003347.4:c.311-2485C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003347.4(UBE2L3):​c.311-2485C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,008 control chromosomes in the GnomAD database, including 3,446 homozygotes. 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: 𝑓 0.18 (3446 hom., cov: 31)
• Consequence: UBE2L3 NM_003347.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220
• Publications: 66 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2L3	NM_003347.4	c.311-2485C>T		intron_variant	Intron 3 of 3	ENST00000342192.9	NP_003338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2L3	ENST00000342192.9	c.311-2485C>T		intron_variant	Intron 3 of 3	1	NM_003347.4	ENSP00000344259.5

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28063 AN: 151890 Hom.: 3440 Cov.: 31

Gnomad AFR AF: 0.0535

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.195

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.185 AC: 28063 AN: 152008 Hom.: 3446 Cov.: 31 AF XY: 0.196 AC XY: 14523 AN XY: 74278

African (AFR) AF: 0.0534 AC: 2215 AN: 41496

American (AMR) AF: 0.305 AC: 4651 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 816 AN: 3466

East Asian (EAS) AF: 0.405 AC: 2084 AN: 5144

South Asian (SAS) AF: 0.267 AC: 1285 AN: 4812

European-Finnish (FIN) AF: 0.322 AC: 3392 AN: 10536

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13024 AN: 67990

Other (OTH) AF: 0.195 AC: 411 AN: 2108

Alfa AF: 0.194 Hom.: 13187

Bravo AF: 0.183

Asia WGS AF: 0.317 AC: 1103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.4
DANN	Benign	0.62
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

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: rs4821116; hg19: chr22-21973319;