8-102270047-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_015902.6(UBR5):c.7222A>G(p.Met2408Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,776 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: 0.0000055 ( 0 hom. )
Consequence
UBR5
NM_015902.6 missense
NM_015902.6 missense
Scores
3
8
8
Clinical Significance
Conservation
PhyloP100: 7.61
Genes affected
UBR5 (HGNC:16806): (ubiquitin protein ligase E3 component n-recognin 5) This gene encodes a progestin-induced protein, which belongs to the HECT (homology to E6-AP carboxyl terminus) family. The HECT family proteins function as E3 ubiquitin-protein ligases, targeting specific proteins for ubiquitin-mediated proteolysis. This gene is localized to chromosome 8q22 which is disrupted in a variety of cancers. This gene potentially has a role in regulation of cell proliferation or differentiation. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, UBR5
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UBR5 | NM_015902.6 | c.7222A>G | p.Met2408Val | missense_variant | 50/59 | ENST00000520539.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UBR5 | ENST00000520539.6 | c.7222A>G | p.Met2408Val | missense_variant | 50/59 | 1 | NM_015902.6 | P5 | |
UBR5 | ENST00000220959.8 | c.7222A>G | p.Met2408Val | missense_variant | 50/59 | 1 | A1 | ||
UBR5 | ENST00000521922.5 | c.7204A>G | p.Met2402Val | missense_variant | 50/59 | 5 | A1 | ||
UBR5 | ENST00000518205.5 | c.409A>G | p.Met137Val | missense_variant | 3/12 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250952Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135612
GnomAD3 exomes
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2
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250952
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AN XY:
135612
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GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461776Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727186
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
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?
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1
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 01, 2023 | The c.7222A>G (p.M2408V) alteration is located in exon 50 (coding exon 50) of the UBR5 gene. This alteration results from a A to G substitution at nucleotide position 7222, causing the methionine (M) at amino acid position 2408 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;T;D
Sift4G
Uncertain
D;D;T;D
Polyphen
B;.;.;B
Vest4
MutPred
Loss of disorder (P = 0.0757);Loss of disorder (P = 0.0757);.;.;
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at