6-89329951-G-C

Variant names:

• chr6-89329951-G-C
• rs10502
• NM_016021.3:c.685C>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.685C>G​(p.Leu229Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,611,968 control chromosomes in the GnomAD database, including 169,668 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.53 (24708 hom., cov: 31)
  • Exomes 𝑓: 0.43 (144960 hom.)
• Consequence: UBE2J1 NM_016021.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.755
• Publications: 36 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 (MetaRNN=8.0727295E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.815 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.685C>G	p.Leu229Val	missense	Exon 8 of 8	NP_057105.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2J1	ENST00000435041.3	TSL:1 MANE Select	c.685C>G	p.Leu229Val	missense	Exon 8 of 8	ENSP00000451261.1

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80768 AN: 151916 Hom.: 24650 Cov.: 31

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.515

GnomAD2 exomes AF: 0.488 AC: 122128 AN: 250154 AF XY: 0.491

Gnomad AFR exome AF: 0.833

Gnomad AMR exome AF: 0.476

Gnomad ASJ exome AF: 0.469

Gnomad EAS exome AF: 0.699

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.372

Gnomad OTH exome AF: 0.439

GnomAD4 exome AF: 0.428 AC: 624541 AN: 1459936 Hom.: 144960 Cov.: 39 AF XY: 0.435 AC XY: 315762 AN XY: 726398

African (AFR) AF: 0.839 AC: 28044 AN: 33442

American (AMR) AF: 0.472 AC: 21110 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 12256 AN: 26116

East Asian (EAS) AF: 0.716 AC: 28418 AN: 39696

South Asian (SAS) AF: 0.736 AC: 63468 AN: 86226

European-Finnish (FIN) AF: 0.332 AC: 17752 AN: 53402

Middle Eastern (MID) AF: 0.544 AC: 3133 AN: 5764

European-Non Finnish (NFE) AF: 0.380 AC: 422166 AN: 1110284

Other (OTH) AF: 0.467 AC: 28194 AN: 60318

GnomAD4 genome AF: 0.532 AC: 80885 AN: 152032 Hom.: 24708 Cov.: 31 AF XY: 0.535 AC XY: 39734 AN XY: 74304

African (AFR) AF: 0.823 AC: 34120 AN: 41468

American (AMR) AF: 0.461 AC: 7035 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1687 AN: 3468

East Asian (EAS) AF: 0.718 AC: 3711 AN: 5170

South Asian (SAS) AF: 0.753 AC: 3633 AN: 4826

European-Finnish (FIN) AF: 0.332 AC: 3505 AN: 10554

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

European-Non Finnish (NFE) AF: 0.376 AC: 25523 AN: 67958

Other (OTH) AF: 0.521 AC: 1102 AN: 2114

Alfa AF: 0.395 Hom.: 9279

Bravo AF: 0.549

TwinsUK AF: 0.370 AC: 1373

ALSPAC AF: 0.377 AC: 1454

ESP6500AA AF: 0.812 AC: 3576

ESP6500EA AF: 0.378 AC: 3251

ExAC AF: 0.495 AC: 60110

Asia WGS AF: 0.742 AC: 2579 AN: 3478

EpiCase AF: 0.385

EpiControl AF: 0.374

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.6
DANN	Benign	0.26
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.063	T
MetaRNN	Benign	8.1e-7	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.76
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.082
Sift	Benign	0.32	T
Sift4G	Benign	0.37	T
Polyphen		0.0	B
Vest4		0.0070
MPC		0.047
ClinPred		0.0044	T
GERP RS		2.7
Varity_R		0.023
gMVP		0.14
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: rs10502; hg19: chr6-90039670; COSMIC: COSV70562172;