22-21562901-G-T

Variant names:

• chr22-21562901-G-T
• rs131654
• NM_001256355.1:c.201+13251G>T

Variant summary

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

The NM_001256355.1(UBE2L3):​c.201+13251G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 151,628 control chromosomes in the GnomAD database, including 43,429 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 0.75 (43429 hom., cov: 28)
• Consequence: UBE2L3 NM_001256355.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 45 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 (AFR) allele frequency at 95% confidence interval = 0.931 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2L3	NM_001256355.1		c.201+13251G>T		intron	N/A	NP_001243284.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2L3	ENST00000458578.6	TSL:2	c.201+13251G>T		intron	N/A	ENSP00000400906.2

Frequencies

GnomAD3 genomes AF: 0.745 AC: 112861 AN: 151512 Hom.: 43351 Cov.: 28

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.765

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

GnomAD4 genome AF: 0.745 AC: 113000 AN: 151628 Hom.: 43429 Cov.: 28 AF XY: 0.744 AC XY: 55110 AN XY: 74056

African (AFR) AF: 0.938 AC: 38851 AN: 41402

American (AMR) AF: 0.727 AC: 11067 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.648 AC: 2247 AN: 3466

East Asian (EAS) AF: 0.566 AC: 2891 AN: 5106

South Asian (SAS) AF: 0.778 AC: 3735 AN: 4802

European-Finnish (FIN) AF: 0.644 AC: 6731 AN: 10454

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45065 AN: 67878

Other (OTH) AF: 0.769 AC: 1617 AN: 2102

Alfa AF: 0.689 Hom.: 156493

Bravo AF: 0.761

Asia WGS AF: 0.742 AC: 2584 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	0.45
DANN	Benign	0.75
PhyloP100		-1.2
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: rs131654; hg19: chr22-21917190;