rs5998672

Variant names:

• chr22-21612153-G-A
• rs5998672
• NM_003347.4:c.310+1110G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-21612153-G-A
• chr22-21612153-G-C

Variant summary

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

The ENST00000342192.9(UBE2L3):​c.310+1110G>A 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 151,976 control chromosomes in the GnomAD database, including 8,393 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 (8393 hom., cov: 31)
• Consequence: UBE2L3 ENST00000342192.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600
• Publications: 21 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000342192.9. 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.310+1110G>A		intron	N/A	NP_003338.1
	UBE2L3	NM_001256355.1		c.484+1110G>A		intron	N/A	NP_001243284.1
	UBE2L3	NM_001256356.2		c.214+1110G>A		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.310+1110G>A		intron	N/A	ENSP00000344259.5
	UBE2L3	ENST00000458578.6	TSL:2	c.484+1110G>A		intron	N/A	ENSP00000400906.2
	UBE2L3	ENST00000545681.2	TSL:2	c.214+1110G>A		intron	N/A	ENSP00000445931.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46896 AN: 151858 Hom.: 8353 Cov.: 31

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.506

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.347

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: 46990 AN: 151976 Hom.: 8393 Cov.: 31 AF XY: 0.320 AC XY: 23784 AN XY: 74284

African (AFR) AF: 0.443 AC: 18332 AN: 41410

American (AMR) AF: 0.357 AC: 5445 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 827 AN: 3470

East Asian (EAS) AF: 0.506 AC: 2622 AN: 5178

South Asian (SAS) AF: 0.395 AC: 1901 AN: 4816

European-Finnish (FIN) AF: 0.347 AC: 3655 AN: 10536

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

European-Non Finnish (NFE) AF: 0.197 AC: 13383 AN: 67994

Other (OTH) AF: 0.293 AC: 621 AN: 2116

Alfa AF: 0.256 Hom.: 2376

Bravo AF: 0.317

Asia WGS AF: 0.499 AC: 1736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.91
DANN	Benign	0.44
PhyloP100		-0.060
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: rs5998672; hg19: chr22-21966442;