chr22-21611009-C-G

Variant names:

• chr22-21611009-C-G
• rs61133050
• NM_003347.4:c.276C>G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_003347.4(UBE2L3):​c.276C>G​(p.Ala92Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00518 in 1,609,566 control chromosomes in the GnomAD database, including 380 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (203 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (177 hom.)
• Consequence: UBE2L3 NM_003347.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.992
• Publications: 3 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 22-21611009-C-G is Benign according to our data. Variant chr22-21611009-C-G is described in ClinVar as Benign. ClinVar VariationId is 781610.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.992 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0924 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.276C>G	p.Ala92Ala	synonymous	Exon 3 of 4	NP_003338.1	P68036-1
	UBE2L3	NM_001256355.1		c.450C>G	p.Ala150Ala	synonymous	Exon 3 of 4	NP_001243284.1	P68036-3
	UBE2L3	NM_001256356.2		c.180C>G	p.Ala60Ala	synonymous	Exon 2 of 3	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.276C>G	p.Ala92Ala	synonymous	Exon 3 of 4	ENSP00000344259.5	P68036-1
	UBE2L3	ENST00000458578.6	TSL:2	c.450C>G	p.Ala150Ala	synonymous	Exon 3 of 4	ENSP00000400906.2	P68036-3
	UBE2L3	ENST00000920161.1		c.276C>G	p.Ala92Ala	synonymous	Exon 3 of 5	ENSP00000590220.1

Frequencies

GnomAD3 genomes AF: 0.0276 AC: 4192 AN: 151976 Hom.: 202 Cov.: 32

Gnomad AFR AF: 0.0948

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0239

GnomAD2 exomes AF: 0.00751 AC: 1852 AN: 246516 AF XY: 0.00552

Gnomad AFR exome AF: 0.0981

Gnomad AMR exome AF: 0.00612

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000279

Gnomad NFE exome AF: 0.000339

Gnomad OTH exome AF: 0.00436

GnomAD4 exome AF: 0.00283 AC: 4123 AN: 1457472 Hom.: 177 Cov.: 31 AF XY: 0.00243 AC XY: 1763 AN XY: 725314

African (AFR) AF: 0.0956 AC: 3158 AN: 33034

American (AMR) AF: 0.00638 AC: 277 AN: 43450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25906

East Asian (EAS) AF: 0.00 AC: 0 AN: 39560

South Asian (SAS) AF: 0.000140 AC: 12 AN: 85742

European-Finnish (FIN) AF: 0.000319 AC: 17 AN: 53330

Middle Eastern (MID) AF: 0.00732 AC: 42 AN: 5734

European-Non Finnish (NFE) AF: 0.000219 AC: 243 AN: 1110580

Other (OTH) AF: 0.00622 AC: 374 AN: 60136

GnomAD4 genome AF: 0.0277 AC: 4207 AN: 152094 Hom.: 203 Cov.: 32 AF XY: 0.0267 AC XY: 1982 AN XY: 74338

African (AFR) AF: 0.0949 AC: 3932 AN: 41444

American (AMR) AF: 0.0128 AC: 195 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10594

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 67998

Other (OTH) AF: 0.0237 AC: 50 AN: 2110

Alfa AF: 0.00162 Hom.: 2

Bravo AF: 0.0318

Asia WGS AF: 0.00549 AC: 20 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	10
DANN	Benign	0.72
PhyloP100		0.99
Mutation Taster		=93/7	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: rs61133050; hg19: chr22-21965298;