22-21577779-C-T

Variant names:

• chr22-21577779-C-T
• rs181362
• NM_003347.4:c.27+10008C>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.27+10008C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,098 control chromosomes in the GnomAD database, including 8,423 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 0.31 (8423 hom., cov: 32)
• Consequence: UBE2L3 NM_003347.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190
• Publications: 104 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

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.27+10008C>T		intron	N/A	NP_003338.1	P68036-1
	UBE2L3	NM_001256355.1		c.202-15082C>T		intron	N/A	NP_001243284.1	P68036-3
	UBE2L3	NM_001256356.2		c.27+10008C>T		intron	N/A	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.27+10008C>T		intron	N/A	ENSP00000344259.5	P68036-1
	UBE2L3	ENST00000458578.6	TSL:2	c.202-15082C>T		intron	N/A	ENSP00000400906.2	P68036-3
	UBE2L3	ENST00000920161.1		c.27+10008C>T		intron	N/A	ENSP00000590220.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46969 AN: 151980 Hom.: 8383 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.309 AC: 47063 AN: 152098 Hom.: 8423 Cov.: 32 AF XY: 0.321 AC XY: 23828 AN XY: 74344

African (AFR) AF: 0.443 AC: 18371 AN: 41480

American (AMR) AF: 0.357 AC: 5452 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 819 AN: 3468

East Asian (EAS) AF: 0.513 AC: 2657 AN: 5176

South Asian (SAS) AF: 0.394 AC: 1901 AN: 4820

European-Finnish (FIN) AF: 0.347 AC: 3666 AN: 10570

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13377 AN: 68002

Other (OTH) AF: 0.292 AC: 616 AN: 2110

Alfa AF: 0.240 Hom.: 15703

Bravo AF: 0.317

Asia WGS AF: 0.502 AC: 1746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.7
DANN	Benign	0.78
PhyloP100		-0.019
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: rs181362; hg19: chr22-21932068;