rs1949453

chr2-181046047-T-Achr2-181046047-T-Cchr2-181046047-T-G

Variant summary

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

The NM_006357.4(UBE2E3):c.246-11646T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,018 control chromosomes in the GnomAD database, including 23,321 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 0.54 (23321 hom., cov: 32)
• Consequence: UBE2E3 NM_006357.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362

Genes affected

UBE2E3 (HGNC:12479): (ubiquitin conjugating enzyme E2 E3) 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, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. The encoded protein shares 100% sequence identity with the mouse and rat counterparts, which indicates that this enzyme is highly conserved in eukaryotes. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jun 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBE2E3	NM_006357.4	c.246-11646T>A		intron_variant		ENST00000410062.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBE2E3	ENST00000410062.9	c.246-11646T>A		intron_variant		1	NM_006357.4	P1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82192 AN: 151898 Hom.: 23265 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.508

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

GnomAD4 genome AF: 0.541 AC: 82308 AN: 152018 Hom.: 23321 Cov.: 32 AF XY: 0.549 AC XY: 40746 AN XY: 74286

Gnomad4 AFR AF: 0.664

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.796

Gnomad4 SAS AF: 0.646

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.513

Alfa AF: 0.376 Hom.: 1077

Bravo AF: 0.551

Asia WGS AF: 0.753 AC: 2617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	4.1
Dann	Benign	0.62

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: rs1949453; hg19: chr2-181910774;