NM_003347.4:c.124-385G>A

Variant names:

• chr22-21610472-G-A
• rs4821112
• NM_003347.4:c.124-385G>A

Variant summary

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

The NM_003347.4(UBE2L3):​c.124-385G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,108 control chromosomes in the GnomAD database, including 4,423 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 0.22 (4423 hom., cov: 32)
• Consequence: UBE2L3 NM_003347.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 55 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2L3	NM_003347.4	c.124-385G>A		intron_variant	Intron 2 of 3	ENST00000342192.9	NP_003338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2L3	ENST00000342192.9	c.124-385G>A		intron_variant	Intron 2 of 3	1	NM_003347.4	ENSP00000344259.5

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33333 AN: 151988 Hom.: 4414 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.219 AC: 33362 AN: 152108 Hom.: 4423 Cov.: 32 AF XY: 0.234 AC XY: 17367 AN XY: 74364

African (AFR) AF: 0.130 AC: 5402 AN: 41516

American (AMR) AF: 0.327 AC: 4993 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 822 AN: 3468

East Asian (EAS) AF: 0.506 AC: 2608 AN: 5152

South Asian (SAS) AF: 0.394 AC: 1893 AN: 4808

European-Finnish (FIN) AF: 0.346 AC: 3668 AN: 10586

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.196 AC: 13293 AN: 67982

Other (OTH) AF: 0.228 AC: 482 AN: 2112

Alfa AF: 0.208 Hom.: 13149

Bravo AF: 0.217

Asia WGS AF: 0.473 AC: 1642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0070
DANN	Benign	0.33
PhyloP100		-1.4
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: rs4821112; hg19: chr22-21964761;