1-1255460-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_058167.3(UBE2J2):​c.523G>C​(p.Asp175His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,611,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

UBE2J2
NM_058167.3 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.51
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27103558).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UBE2J2NM_058167.3 linkc.523G>C p.Asp175His missense_variant Exon 7 of 7 ENST00000349431.11 NP_477515.2 Q8N2K1-1A0A024R075

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UBE2J2ENST00000349431.11 linkc.523G>C p.Asp175His missense_variant Exon 7 of 7 1 NM_058167.3 ENSP00000305826.7 Q8N2K1-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152228
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000805
AC:
2
AN:
248346
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134446
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000328
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1459228
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
725386
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.01e-7
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152228
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000453

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 14, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.571G>C (p.D191H) alteration is located in exon 8 (coding exon 7) of the UBE2J2 gene. This alteration results from a G to C substitution at nucleotide position 571, causing the aspartic acid (D) at amino acid position 191 to be replaced by a histidine (H). 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
0.15
BayesDel_addAF
Benign
-0.015
T
BayesDel_noAF
Benign
-0.26
CADD
Uncertain
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.022
T;T;T;T;.;T;.
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.94
D;.;.;D;D;D;D
M_CAP
Benign
0.050
D
MetaRNN
Benign
0.27
T;T;T;T;T;T;T
MetaSVM
Benign
-0.57
T
MutationAssessor
Benign
1.1
.;L;.;L;.;.;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-1.6
N;N;N;N;N;N;.
REVEL
Benign
0.13
Sift
Uncertain
0.023
D;D;D;D;D;D;.
Sift4G
Benign
0.11
T;T;T;T;T;D;.
Polyphen
0.34
B;B;B;B;.;.;.
Vest4
0.15
MutPred
0.19
.;Loss of helix (P = 0.0444);.;Loss of helix (P = 0.0444);.;Loss of helix (P = 0.0444);.;
MVP
0.84
MPC
1.3
ClinPred
0.44
T
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.22
gMVP
0.43

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs1039214256; hg19: chr1-1190840; API