22-21585386-G-T

Variant names:

• chr22-21585386-G-T
• rs5754217
• NM_003347.4:c.28-7475G>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.28-7475G>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 151,998 control chromosomes in the GnomAD database, including 8,412 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 (8412 hom., cov: 32)
• Consequence: UBE2L3 NM_003347.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.724
• Publications: 122 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2L3	NM_003347.4	MANE Select	c.28-7475G>T		intron	N/A	NP_003338.1
	UBE2L3	NM_001256355.1		c.202-7475G>T		intron	N/A	NP_001243284.1
	UBE2L3	NM_001256356.2		c.27+17615G>T		intron	N/A	NP_001243285.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2L3	ENST00000342192.9	TSL:1 MANE Select	c.28-7475G>T		intron	N/A	ENSP00000344259.5
	UBE2L3	ENST00000458578.6	TSL:2	c.202-7475G>T		intron	N/A	ENSP00000400906.2
	UBE2L3	ENST00000545681.2	TSL:2	c.27+17615G>T		intron	N/A	ENSP00000445931.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46941 AN: 151880 Hom.: 8372 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.309 AC: 47035 AN: 151998 Hom.: 8412 Cov.: 32 AF XY: 0.321 AC XY: 23814 AN XY: 74298

African (AFR) AF: 0.443 AC: 18367 AN: 41462

American (AMR) AF: 0.357 AC: 5453 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 819 AN: 3472

East Asian (EAS) AF: 0.515 AC: 2661 AN: 5172

South Asian (SAS) AF: 0.395 AC: 1903 AN: 4820

European-Finnish (FIN) AF: 0.346 AC: 3652 AN: 10546

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

European-Non Finnish (NFE) AF: 0.197 AC: 13357 AN: 67942

Other (OTH) AF: 0.293 AC: 619 AN: 2112

Alfa AF: 0.236 Hom.: 22864

Bravo AF: 0.317

Asia WGS AF: 0.502 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.17
DANN	Benign	0.43
PhyloP100		-0.72
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: rs5754217; hg19: chr22-21939675;