1-1256050-C-G

Variant names:

• chr1-1256050-C-G
• rs376025644
• NM_058167.3:c.490G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_058167.3(UBE2J2):​c.490G>C​(p.Val164Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. V164M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: UBE2J2 NM_058167.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.23
• Publications: 3 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25822222).

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.490G>C	p.Val164Leu	missense	Exon 6 of 7	NP_477515.2
	UBE2J2	NM_194315.2		c.538G>C	p.Val180Leu	missense	Exon 7 of 8	NP_919296.1	Q8N2K1-3
	UBE2J2	NM_194457.2		c.334G>C	p.Val112Leu	missense	Exon 5 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.490G>C	p.Val164Leu	missense	Exon 6 of 7	ENSP00000305826.7	Q8N2K1-1
	UBE2J2	ENST00000400930.8	TSL:5	c.538G>C	p.Val180Leu	missense	Exon 7 of 8	ENSP00000383719.4	Q8N2K1-3
	UBE2J2	ENST00000360466.6	TSL:2	c.490G>C	p.Val164Leu	missense	Exon 6 of 7	ENSP00000353653.2	Q8N2K1-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.045
Eigen_PC	Benign	0.071
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		5.2
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.12
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.031	D
Polyphen		0.20	B
Vest4		0.61
MutPred		0.26		Loss of helix (P = 0.0558)
MVP		0.42
MPC		0.92
ClinPred		0.87	D
GERP RS		3.7
Varity_R		0.52
gMVP		0.69
Mutation Taster		=57/43	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs376025644; hg19: chr1-1191430;