4-102838032-T-C

Variant names:

• chr4-102838032-T-C
• rs223371
• NM_181893.3:c.31-28177A>G

Variant summary

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

The NM_181893.3(UBE2D3):​c.31-28177A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 151,750 control chromosomes in the GnomAD database, including 25,027 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 0.56 (25027 hom., cov: 30)
• Consequence: UBE2D3 NM_181893.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 9 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]

UBE2D3-AS1 (HGNC:54095): (UBE2D3 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2D3	NM_181893.3	c.31-28177A>G		intron_variant	Intron 1 of 6		NP_871622.1
UBE2D3	NM_181890.3	c.-128-11396A>G		intron_variant	Intron 1 of 7		NP_871619.1
UBE2D3-AS1	NR_131185.1	n.187-2677T>C		intron_variant	Intron 1 of 2
UBE2D3-AS1	NR_131186.1	n.132-5292T>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2D3	ENST00000357194.10	c.31-28177A>G		intron_variant	Intron 1 of 6	2		ENSP00000349722.6
UBE2D3	ENST00000338145.7	c.-128-11396A>G		intron_variant	Intron 1 of 7	5		ENSP00000337208.3
UBE2D3	ENST00000508238.5	c.-111-11413A>G		intron_variant	Intron 1 of 5	4		ENSP00000423487.1

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85296 AN: 151632 Hom.: 24993 Cov.: 30

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.563 AC: 85377 AN: 151750 Hom.: 25027 Cov.: 30 AF XY: 0.562 AC XY: 41674 AN XY: 74160

African (AFR) AF: 0.740 AC: 30606 AN: 41370

American (AMR) AF: 0.569 AC: 8688 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1798 AN: 3466

East Asian (EAS) AF: 0.523 AC: 2694 AN: 5154

South Asian (SAS) AF: 0.500 AC: 2401 AN: 4802

European-Finnish (FIN) AF: 0.466 AC: 4902 AN: 10520

Middle Eastern (MID) AF: 0.562 AC: 164 AN: 292

European-Non Finnish (NFE) AF: 0.477 AC: 32411 AN: 67878

Other (OTH) AF: 0.568 AC: 1195 AN: 2104

Alfa AF: 0.537 Hom.: 2883

Bravo AF: 0.579

Asia WGS AF: 0.521 AC: 1813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.89
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs223371; hg19: chr4-103759189;