9-6413540-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152896.3(UHRF2):ā€‹c.50A>Gā€‹(p.Glu17Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,443,914 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 (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

UHRF2
NM_152896.3 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.32
Variant links:
Genes affected
UHRF2 (HGNC:12557): (ubiquitin like with PHD and ring finger domains 2) This gene encodes a nuclear protein which is involved in cell-cycle regulation. The encoded protein is a ubiquitin-ligase capable of ubiquinating PCNP (PEST-containing nuclear protein), and together they may play a role in tumorigenesis. The encoded protein contains an NIRF_N domain, a PHD finger, a set- and ring-associated (SRA) domain, and a RING finger domain and several of these domains have been shown to be essential for the regulation of cell proliferation. This protein may also have a role in intranuclear degradation of polyglutamine aggregates. Alternative splicing results in multiple transcript variants some of which are non-protein coding. [provided by RefSeq, Feb 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.16919029).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
UHRF2NM_152896.3 linkc.50A>G p.Glu17Gly missense_variant 1/16 ENST00000276893.10 NP_690856.1 Q96PU4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
UHRF2ENST00000276893.10 linkc.50A>G p.Glu17Gly missense_variant 1/161 NM_152896.3 ENSP00000276893.5 Q96PU4-1
UHRF2ENST00000468435.6 linkn.50A>G non_coding_transcript_exon_variant 1/171 ENSP00000434182.1 Q96PU4-2
UHRF2ENST00000381373.3 linkc.50A>G p.Glu17Gly missense_variant 1/33 ENSP00000370778.3 B1AL33
UHRF2ENST00000469298.5 linkn.221A>G non_coding_transcript_exon_variant 2/45

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000856
AC:
2
AN:
233654
Hom.:
0
AF XY:
0.00000786
AC XY:
1
AN XY:
127182
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000124
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000208
AC:
3
AN:
1443914
Hom.:
0
Cov.:
31
AF XY:
0.00000418
AC XY:
3
AN XY:
718236
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000266
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.06e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsDec 15, 2023The c.50A>G (p.E17G) alteration is located in exon 1 (coding exon 1) of the UHRF2 gene. This alteration results from a A to G substitution at nucleotide position 50, causing the glutamic acid (E) at amino acid position 17 to be replaced by a glycine (G). 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
0.32
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T;T
Eigen
Benign
-0.12
Eigen_PC
Benign
0.0063
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.73
T;T
M_CAP
Benign
0.057
D
MetaRNN
Benign
0.17
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L;.
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-2.1
N;D
REVEL
Benign
0.13
Sift
Benign
0.10
T;T
Sift4G
Benign
0.10
T;D
Polyphen
0.0090
B;.
Vest4
0.34
MutPred
0.58
Loss of stability (P = 0.0402);Loss of stability (P = 0.0402);
MVP
0.12
MPC
1.8
ClinPred
0.57
D
GERP RS
3.8
Varity_R
0.14
gMVP
0.71

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

LitVar

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

Other links and lift over

dbSNP: rs753459104; hg19: chr9-6413540; API