Genetic Variant UBE2L3:c.*976T>C (chr22-21622645-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003347.4(UBE2L3):c.*976T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 153,146 control chromosomes in the GnomAD database, including 9,374 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 0.32 ( 9320 hom., cov: 32)

Exomes 𝑓: 0.29 ( 54 hom. )

Consequence

UBE2L3
NM_003347.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.317

Publications

73 publications found

Variant links:

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

UBE2L3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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: NM_003347.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
UBE2L3	NM_003347.4	MANE Select	c.*976T>C	3_prime_UTR	Exon 4 of 4	NP_003338.1
UBE2L3	NR_028436.3		n.1581T>C	non_coding_transcript_exon	Exon 5 of 5
UBE2L3	NR_046082.2		n.2078T>C	non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
UBE2L3	ENST00000342192.9	TSL:1 MANE Select	c.*976T>C	3_prime_UTR	Exon 4 of 4	ENSP00000344259.5
UBE2L3	ENST00000496722.1	TSL:2	n.2062T>C	non_coding_transcript_exon	Exon 4 of 4
UBE2L3	ENST00000458578.6	TSL:2	c.*976T>C	3_prime_UTR	Exon 4 of 4	ENSP00000400906.2

Frequencies

GnomAD3 genomes

AF:

0.322

AC:

48987

AN:

151960

Hom.:

9277

Cov.:

show subpopulations

Gnomad AFR

AF:

0.489

Gnomad AMI

AF:

0.141

Gnomad AMR

AF:

0.362

Gnomad ASJ

AF:

0.239

Gnomad EAS

AF:

0.505

Gnomad SAS

AF:

0.397

Gnomad FIN

AF:

0.346

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.197

Gnomad OTH

AF:

0.296

GnomAD4 exome

AF:

0.289

AC:

309

AN:

1068

Hom.:

Cov.:

AF XY:

0.301

AC XY:

181

AN XY:

602

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.300

AC:

AN:

East Asian (EAS)

AF:

0.289

AC:

AN:

232

South Asian (SAS)

AF:

0.750

AC:

AN:

European-Finnish (FIN)

AF:

0.346

AC:

106

AN:

306

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.239

AC:

109

AN:

456

Other (OTH)

AF:

0.289

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.323

AC:

49083

AN:

152078

Hom.:

9320

Cov.:

AF XY:

0.333

AC XY:

24786

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.490

AC:

20312

AN:

41478

American (AMR)

AF:

0.363

AC:

5546

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

829

AN:

3470

East Asian (EAS)

AF:

0.506

AC:

2611

AN:

5162

South Asian (SAS)

AF:

0.394

AC:

1900

AN:

4820

European-Finnish (FIN)

AF:

0.346

AC:

3658

AN:

10568

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.197

AC:

13383

AN:

67976

Other (OTH)

AF:

0.302

AC:

638

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1583

3167

4750

6334

7917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

474

948

1422

1896

2370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.254

Hom.:

6931

Bravo

AF:

0.333

Asia WGS

AF:

0.502

AC:

1745

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

7.3

(source)

DANN

Benign

0.58

PhyloP100

0.32

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over