rs2266961

Variant names:

• chr22-21574308-C-G
• rs2266961
• NM_003347.4:c.27+6537C>G

Variant summary

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

The NM_003347.4(UBE2L3):​c.27+6537C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,194 control chromosomes in the GnomAD database, including 3,503 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 0.19 (3503 hom., cov: 32)
• Consequence: UBE2L3 NM_003347.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.411
• Publications: 28 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2L3	NM_003347.4	c.27+6537C>G		intron_variant	Intron 1 of 3	ENST00000342192.9	NP_003338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2L3	ENST00000342192.9	c.27+6537C>G		intron_variant	Intron 1 of 3	1	NM_003347.4	ENSP00000344259.5

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28500 AN: 152076 Hom.: 3497 Cov.: 32

Gnomad AFR AF: 0.0607

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.187 AC: 28503 AN: 152194 Hom.: 3503 Cov.: 32 AF XY: 0.199 AC XY: 14778 AN XY: 74408

African (AFR) AF: 0.0607 AC: 2522 AN: 41558

American (AMR) AF: 0.306 AC: 4672 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 809 AN: 3468

East Asian (EAS) AF: 0.413 AC: 2139 AN: 5176

South Asian (SAS) AF: 0.276 AC: 1332 AN: 4818

European-Finnish (FIN) AF: 0.322 AC: 3399 AN: 10570

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

European-Non Finnish (NFE) AF: 0.192 AC: 13031 AN: 68000

Other (OTH) AF: 0.196 AC: 414 AN: 2108

Alfa AF: 0.179 Hom.: 355

Bravo AF: 0.186

Asia WGS AF: 0.327 AC: 1137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.70
PhyloP100		0.41
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: rs2266961; hg19: chr22-21928597;