GeneBe

rs769541649

Variant names:

Variant summary

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

The NM_003338.5(UBE2D1):​c.43C>G​(p.Arg15Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R15C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

UBE2D1
NM_003338.5 missense

Scores

3
8
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.40

Publications

2 publications found
Variant links:
Genes affected
UBE2D1 (HGNC:12474): (ubiquitin conjugating enzyme E2 D1) 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 closely related to a stimulator of iron transport (SFT), and is up-regulated in hereditary hemochromatosis. It also functions in the ubiquitination of the tumor-suppressor protein p53 and the hypoxia-inducible transcription factor HIF1alpha by interacting with the E1 ubiquitin-activating enzyme and the E3 ubiquitin-protein ligases. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003338.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
UBE2D1
NM_003338.5
MANE Select
c.43C>Gp.Arg15Gly
missense
Exon 2 of 7NP_003329.1P51668
UBE2D1
NM_001204880.2
c.-40C>G
5_prime_UTR
Exon 2 of 6NP_001191809.1A0A087WW00

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
UBE2D1
ENST00000373910.9
TSL:1 MANE Select
c.43C>Gp.Arg15Gly
missense
Exon 2 of 7ENSP00000363019.3P51668
UBE2D1
ENST00000909472.1
c.43C>Gp.Arg15Gly
missense
Exon 2 of 7ENSP00000579531.1
UBE2D1
ENST00000909473.1
c.43C>Gp.Arg15Gly
missense
Exon 2 of 6ENSP00000579532.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.58
BayesDel_addAF
Uncertain
0.079
D
BayesDel_noAF
Benign
-0.12
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.25
T
Eigen
Uncertain
0.27
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.045
D
MetaRNN
Uncertain
0.55
D
MetaSVM
Benign
-0.83
T
MutationAssessor
Uncertain
2.3
M
PhyloP100
2.4
PrimateAI
Pathogenic
0.89
D
PROVEAN
Pathogenic
-4.8
D
REVEL
Benign
0.22
Sift
Uncertain
0.0010
D
Sift4G
Benign
0.098
T
Polyphen
0.18
B
Vest4
0.71
MutPred
0.38
Loss of solvent accessibility (P = 0.0044)
MVP
0.79
MPC
1.3
ClinPred
0.97
D
GERP RS
6.1
Varity_R
0.90
gMVP
0.78
Mutation Taster
=41/59
disease causing

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs769541649; hg19: chr10-60121116; API