1-1255351-C-A

Variant names:

• chr1-1255351-C-A
• rs900199328
• NM_058167.3:c.632G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_058167.3(UBE2J2):​c.632G>T​(p.Gly211Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. G211A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UBE2J2 NM_058167.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.17
• Publications: 0 publications found

Genes affected

UBE2J2 (HGNC:19268): (ubiquitin conjugating enzyme E2 J2) 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. Multiple alternatively spliced transcript variants have been found for this gene, but the full-length nature of some variants has not been defined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06779739).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058167.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2J2	NM_058167.3	MANE Select	c.632G>T	p.Gly211Val	missense	Exon 7 of 7	NP_477515.2
	UBE2J2	NM_194315.2		c.680G>T	p.Gly227Val	missense	Exon 8 of 8	NP_919296.1	Q8N2K1-3
	UBE2J2	NM_194457.2		c.476G>T	p.Gly159Val	missense	Exon 6 of 6	NP_919439.1	A6NGS0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBE2J2	ENST00000349431.11	TSL:1 MANE Select	c.632G>T	p.Gly211Val	missense	Exon 7 of 7	ENSP00000305826.7	Q8N2K1-1
	UBE2J2	ENST00000400930.8	TSL:5	c.680G>T	p.Gly227Val	missense	Exon 8 of 8	ENSP00000383719.4	Q8N2K1-3
	UBE2J2	ENST00000360466.6	TSL:2	c.632G>T	p.Gly211Val	missense	Exon 7 of 7	ENSP00000353653.2	Q8N2K1-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461424 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726992

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	10
DANN	Benign	0.89
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.2
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.025
Sift	Benign	0.17	T
Sift4G	Benign	0.12	T
Polyphen		0.044	B
Vest4		0.072
MutPred		0.42		Loss of disorder (P = 0.046)
MVP		0.76
MPC		0.90
ClinPred		0.086	T
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.050
gMVP		0.42
Mutation Taster		=85/15	polymorphism

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: rs900199328; hg19: chr1-1190731;