1-10072113-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BS2

The NM_001105562.3(UBE4B):​c.110C>T​(p.Pro37Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,444 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

UBE4B
NM_001105562.3 missense

Scores

2
9
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.31
Variant links:
Genes affected
UBE4B (HGNC:12500): (ubiquitination factor E4B) 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 an additional conjugation factor, E4, which is involved in multiubiquitin chain assembly. This gene is also the strongest candidate in the neuroblastoma tumor suppressor genes. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UBE4BNM_001105562.3 linkc.110C>T p.Pro37Leu missense_variant Exon 2 of 28 ENST00000343090.11 NP_001099032.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UBE4BENST00000343090.11 linkc.110C>T p.Pro37Leu missense_variant Exon 2 of 28 1 NM_001105562.3 ENSP00000343001.6 O95155-1
UBE4BENST00000253251.12 linkc.110C>T p.Pro37Leu missense_variant Exon 2 of 27 1 ENSP00000253251.8 O95155-2
UBE4BENST00000672724.1 linkc.110C>T p.Pro37Leu missense_variant Exon 2 of 29 ENSP00000500453.1 O95155-4
UBE4BENST00000377153.5 linkc.110C>T p.Pro37Leu missense_variant Exon 2 of 3 3 ENSP00000366358.1 B1AQ61

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250782
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135586
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:
0.0000328
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461444
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
727032
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 28, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.110C>T (p.P37L) alteration is located in exon 2 (coding exon 2) of the UBE4B gene. This alteration results from a C to T substitution at nucleotide position 110, causing the proline (P) at amino acid position 37 to be replaced by a leucine (L). 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
0.14
BayesDel_addAF
Uncertain
0.055
T
BayesDel_noAF
Benign
-0.16
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.10
.;T;T
Eigen
Uncertain
0.24
Eigen_PC
Benign
0.21
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.99
D;D;D
M_CAP
Uncertain
0.10
D
MetaRNN
Uncertain
0.48
T;T;T
MetaSVM
Benign
-0.49
T
MutationAssessor
Benign
1.7
L;.;L
PrimateAI
Uncertain
0.75
T
PROVEAN
Uncertain
-2.5
D;D;N
REVEL
Uncertain
0.38
Sift
Benign
0.040
D;D;D
Sift4G
Uncertain
0.013
D;D;D
Polyphen
1.0
D;.;D
Vest4
0.60
MutPred
0.26
Loss of glycosylation at P37 (P = 0.0429);Loss of glycosylation at P37 (P = 0.0429);Loss of glycosylation at P37 (P = 0.0429);
MVP
0.41
MPC
0.78
ClinPred
0.92
D
GERP RS
4.5
Varity_R
0.26
gMVP
0.65

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

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

Other links and lift over

dbSNP: rs1212128708; hg19: chr1-10132171; API