NM_016021.3:c.429-1254A>G

Variant names:

• chr6-89336685-T-C
• rs12189673
• NM_016021.3:c.429-1254A>G

Variant summary

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

The NM_016021.3(UBE2J1):​c.429-1254A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 151,820 control chromosomes in the GnomAD database, including 5,385 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 0.24 (5385 hom., cov: 29)
• Consequence: UBE2J1 NM_016021.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.923
• Publications: 6 publications found

Genes affected

UBE2J1 (HGNC:17598): (ubiquitin conjugating enzyme E2 J1) 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 is located in the membrane of the endoplasmic reticulum (ER) and may contribute to quality control ER-associated degradation by the ubiquitin-proteasome system. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016021.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2J1	NM_016021.3	MANE Select	c.429-1254A>G		intron	N/A	NP_057105.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2J1	ENST00000435041.3	TSL:1 MANE Select	c.429-1254A>G		intron	N/A	ENSP00000451261.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36398 AN: 151702 Hom.: 5382 Cov.: 29

Gnomad AFR AF: 0.0704

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.240 AC: 36397 AN: 151820 Hom.: 5385 Cov.: 29 AF XY: 0.239 AC XY: 17694 AN XY: 74166

African (AFR) AF: 0.0703 AC: 2914 AN: 41460

American (AMR) AF: 0.327 AC: 4982 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1003 AN: 3466

East Asian (EAS) AF: 0.272 AC: 1405 AN: 5168

South Asian (SAS) AF: 0.169 AC: 813 AN: 4818

European-Finnish (FIN) AF: 0.294 AC: 3077 AN: 10458

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21455 AN: 67906

Other (OTH) AF: 0.242 AC: 511 AN: 2108

Alfa AF: 0.286 Hom.: 12361

Bravo AF: 0.240

Asia WGS AF: 0.195 AC: 675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	12
DANN	Benign	0.58
PhyloP100		0.92
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: rs12189673; hg19: chr6-90046404;