rs223392

Variant names:

• chr4-102824599-A-G
• rs223392
• NM_181891.3:c.24+1886T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181891.3(UBE2D3):​c.24+1886T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 152,100 control chromosomes in the GnomAD database, including 26,414 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 0.57 (26414 hom., cov: 32)
• Consequence: UBE2D3 NM_181891.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.448
• Publications: 11 publications found

Genes affected

UBE2D3 (HGNC:12476): (ubiquitin conjugating enzyme E2 D3) 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. This enzyme functions in the ubiquitination of the tumor-suppressor protein p53, which is induced by an E3 ubiquitin-protein ligase. [provided by RefSeq, Jan 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2D3	NM_181891.3	c.24+1886T>C		intron_variant	Intron 2 of 7	ENST00000453744.7	NP_871620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2D3	ENST00000453744.7	c.24+1886T>C		intron_variant	Intron 2 of 7	1	NM_181891.3	ENSP00000396901.2

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87305 AN: 151982 Hom.: 26368 Cov.: 32

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.575 AC: 87406 AN: 152100 Hom.: 26414 Cov.: 32 AF XY: 0.574 AC XY: 42679 AN XY: 74358

African (AFR) AF: 0.776 AC: 32178 AN: 41480

American (AMR) AF: 0.576 AC: 8808 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1805 AN: 3472

East Asian (EAS) AF: 0.523 AC: 2707 AN: 5180

South Asian (SAS) AF: 0.503 AC: 2430 AN: 4830

European-Finnish (FIN) AF: 0.466 AC: 4926 AN: 10570

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32645 AN: 67956

Other (OTH) AF: 0.575 AC: 1214 AN: 2110

Alfa AF: 0.545 Hom.: 2991

Bravo AF: 0.593

Asia WGS AF: 0.528 AC: 1837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.63
PhyloP100		0.45
Mutation Taster		=100/0	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: rs223392; hg19: chr4-103745756;