6-89329759-T-C

Position:

• chr6-89329759-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016021.3(UBE2J1):​c.877A>G​(p.Ile293Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: UBE2J1 NM_016021.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.59

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.104020804).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2J1	NM_016021.3	c.877A>G	p.Ile293Val	missense_variant	8/8	ENST00000435041.3	NP_057105.2
UBE2J1	XM_011535887.3	c.757A>G	p.Ile253Val	missense_variant	7/7		XP_011534189.1
UBE2J1	XM_011535888.4	c.*199A>G		3_prime_UTR_variant	8/8		XP_011534190.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2J1	ENST00000435041.3	c.877A>G	p.Ile293Val	missense_variant	8/8	1	NM_016021.3	ENSP00000451261	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2023

The c.877A>G (p.I293V) alteration is located in exon 8 (coding exon 8) of the UBE2J1 gene. This alteration results from a A to G substitution at nucleotide position 877, causing the isoleucine (I) at amino acid position 293 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	0.95	D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.054
Sift	Benign	0.55	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.058
MutPred		0.26		Loss of helix (P = 0.0558);
MVP		0.21
MPC		0.042
ClinPred		0.085	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.024
gMVP		0.35

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: rs1350425806; hg19: chr6-90039478;