6-89336685-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2J1	NM_016021.3	c.429-1254A>G		intron_variant	Intron 5 of 7	ENST00000435041.3	NP_057105.2
UBE2J1	XM_011535887.3	c.429-1254A>G		intron_variant	Intron 5 of 6		XP_011534189.1
UBE2J1	XM_011535888.4	c.429-1254A>G		intron_variant	Intron 5 of 7		XP_011534190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2J1	ENST00000435041.3	c.429-1254A>G		intron_variant	Intron 5 of 7	1	NM_016021.3	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

Gnomad4 AFR AF: 0.0703

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.272

Gnomad4 SAS AF: 0.169

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.242

Alfa AF: 0.290 Hom.: 9094

Bravo AF: 0.240

Asia WGS AF: 0.195 AC: 675 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	12
DANN	Benign	0.58

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: rs12189673; hg19: chr6-90046404;