dbSNP rs7444: 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2L3	NM_003347.4 link	c.*976T>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000342192.9	NP_003338.1	P68036-1A0A024R1A4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
UBE2L3	ENST00000342192.9 link	c.*976T>C	3_prime_UTR_variant	Exon 4 of 4	1	NM_003347.4	ENSP00000344259.5	P68036-1
UBE2L3	ENST00000496722.1 link	n.2062T>C	non_coding_transcript_exon_variant	Exon 4 of 4	2
UBE2L3	ENST00000458578.6 link	c.*976T>C	3_prime_UTR_variant	Exon 4 of 4	2		ENSP00000400906.2	P68036-3
UBE2L3	ENST00000545681.2 link	c.*976T>C	3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000445931.1	P68036-2

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over