rs5998672

Positions:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003347.4(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 NM_003347.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
UBE2L3	NM_003347.4	c.310+1110G>A		intron_variant		ENST00000342192.9	NP_003338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2L3	ENST00000342192.9	c.310+1110G>A		intron_variant		1	NM_003347.4	ENSP00000344259	P1

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

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.506

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.293

Alfa AF: 0.237 Hom.: 1153

Bravo AF: 0.317

Asia WGS AF: 0.499 AC: 1736 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	0.91
DANN	Benign	0.44

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

LitVar

Other links and lift over

dbSNP: rs5998672; hg19: chr22-21966442;