9-6477636-G-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_152896.3(UHRF2):ā€‹c.988G>Cā€‹(p.Glu330Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000869 in 1,611,874 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: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000089 ( 0 hom. )

Consequence

UHRF2
NM_152896.3 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.01
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 Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.42012602).
BS2
High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
UHRF2NM_152896.3 linkc.988G>C p.Glu330Gln missense_variant 6/16 ENST00000276893.10 NP_690856.1 Q96PU4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
UHRF2ENST00000276893.10 linkc.988G>C p.Glu330Gln missense_variant 6/161 NM_152896.3 ENSP00000276893.5 Q96PU4-1
UHRF2ENST00000468435.6 linkn.988G>C non_coding_transcript_exon_variant 6/171 ENSP00000434182.1 Q96PU4-2
UHRF2ENST00000450508.1 linkc.319G>C p.Glu107Gln missense_variant 4/43 ENSP00000399217.2 A0A0A0MSQ3
UHRF2ENST00000484159.5 linkn.430G>C non_coding_transcript_exon_variant 4/82

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152194
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249404
Hom.:
0
AF XY:
0.00000742
AC XY:
1
AN XY:
134752
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:
0.00000886
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000891
AC:
13
AN:
1459680
Hom.:
0
Cov.:
30
AF XY:
0.00000964
AC XY:
7
AN XY:
726046
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152194
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

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 GeneticsJun 30, 2024The c.988G>C (p.E330Q) alteration is located in exon 6 (coding exon 6) of the UHRF2 gene. This alteration results from a G to C substitution at nucleotide position 988, causing the glutamic acid (E) at amino acid position 330 to be replaced by a glutamine (Q). 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
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.12
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T;T
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Benign
0.76
T;T
M_CAP
Uncertain
0.093
D
MetaRNN
Benign
0.42
T;T
MetaSVM
Uncertain
0.29
D
MutationAssessor
Uncertain
2.4
M;.
PrimateAI
Benign
0.48
T
PROVEAN
Benign
-1.4
N;N
REVEL
Uncertain
0.34
Sift
Benign
0.29
T;D
Sift4G
Benign
0.35
T;D
Polyphen
0.98
D;.
Vest4
0.41
MVP
0.79
MPC
1.6
ClinPred
0.75
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8
Varity_R
0.24
gMVP
0.63

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: rs1336129287; hg19: chr9-6477636; API