Genetic Variant NM_016021.3:c.685C>G (chr6-89329951-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.53 ( 24708 hom., cov: 31)

Exomes 𝑓: 0.43 ( 144960 hom. )

Consequence

UBE2J1
NM_016021.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.755

Variant links:

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]

UBE2J1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2J1	NM_016021.3 link	c.685C>G	p.Leu229Val	missense_variant	Exon 8 of 8	ENST00000435041.3	NP_057105.2	Q9Y385
UBE2J1	XM_011535887.3 link	c.565C>G	p.Leu189Val	missense_variant	Exon 7 of 7		XP_011534189.1
UBE2J1	XM_011535888.4 link	c.*7C>G		3_prime_UTR_variant	Exon 8 of 8		XP_011534190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2J1	ENST00000435041.3 link	c.685C>G	p.Leu229Val	missense_variant	Exon 8 of 8	1	NM_016021.3	ENSP00000451261.1		Q9Y385

Frequencies

GnomAD3 genomes

AF:

0.532

AC:

80768

AN:

151916

Hom.:

24650

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.488

AC:

122128

AN:

250154

Hom.:

33374

AF XY:

0.491

AC XY:

66412

AN XY:

135334

show subpopulations

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 SAS exome

AF:

0.745

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.:

AF XY:

0.435

AC XY:

315762

AN XY:

726398

show subpopulations

Gnomad4 AFR exome

AF:

0.839

Gnomad4 AMR exome

AF:

0.472

Gnomad4 ASJ exome

AF:

0.469

Gnomad4 EAS exome

AF:

0.716

Gnomad4 SAS exome

AF:

0.736

Gnomad4 FIN exome

AF:

0.332

Gnomad4 NFE exome

AF:

0.380

Gnomad4 OTH exome

AF:

0.467

GnomAD4 genome

AF:

0.532

AC:

80885

AN:

152032

Hom.:

24708

Cov.:

AF XY:

0.535

AC XY:

39734

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.823

Gnomad4 AMR

AF:

0.461

Gnomad4 ASJ

AF:

0.486

Gnomad4 EAS

AF:

0.718

Gnomad4 SAS

AF:

0.753

Gnomad4 FIN

AF:

0.332

Gnomad4 NFE

AF:

0.376

Gnomad4 OTH

AF:

0.521

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

3.6

DANN

Benign

0.26

DEOGEN2

Benign

0.0052

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0018

LIST_S2

Benign

0.063

MetaRNN

Benign

8.1e-7

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.27

PROVEAN

Benign

0.19

REVEL

Benign

0.082

Sift

Benign

0.32

Sift4G

Benign

0.37

Polyphen

0.0

Vest4

0.0070

MPC

0.047

ClinPred

0.0044

GERP RS

2.7

Varity_R

0.023

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over