22-21566528-G-C

Variant names:

• chr22-21566528-G-C
• rs59391722
• NM_001256355.1:c.201+16878G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001256355.1(UBE2L3):​c.201+16878G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 151,466 control chromosomes in the GnomAD database, including 3,419 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (3419 hom., cov: 29)
• Consequence: UBE2L3 NM_001256355.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.248
• Publications: 17 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 22-21566528-G-C is Benign according to our data. Variant chr22-21566528-G-C is described in ClinVar as Benign. ClinVar VariationId is 1291200.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256355.1. 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_001256355.1		c.201+16878G>C		intron	N/A	NP_001243284.1	P68036-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2L3	ENST00000458578.6	TSL:2	c.201+16878G>C		intron	N/A	ENSP00000400906.2	P68036-3

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27899 AN: 151348 Hom.: 3413 Cov.: 29

Gnomad AFR AF: 0.0528

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.410

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.184 AC: 27898 AN: 151466 Hom.: 3419 Cov.: 29 AF XY: 0.195 AC XY: 14421 AN XY: 73946

African (AFR) AF: 0.0527 AC: 2180 AN: 41382

American (AMR) AF: 0.304 AC: 4613 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 807 AN: 3464

East Asian (EAS) AF: 0.411 AC: 2091 AN: 5088

South Asian (SAS) AF: 0.277 AC: 1330 AN: 4806

European-Finnish (FIN) AF: 0.319 AC: 3302 AN: 10366

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

European-Non Finnish (NFE) AF: 0.191 AC: 12984 AN: 67872

Other (OTH) AF: 0.194 AC: 406 AN: 2096

Alfa AF: 0.0908 Hom.: 127

Bravo AF: 0.183

Asia WGS AF: 0.327 AC: 1135 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
DANN	Benign	0.47
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs59391722; hg19: chr22-21920817; COSMIC: COSV60537969; COSMIC: COSV60537969;