9-6477625-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_152896.3(UHRF2):​c.977G>A​(p.Arg326Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000106 in 1,603,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

UHRF2
NM_152896.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.97
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 -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.07278213).
BS2
High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
UHRF2NM_152896.3 linkuse as main transcriptc.977G>A p.Arg326Gln 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 linkuse as main transcriptc.977G>A p.Arg326Gln missense_variant 6/161 NM_152896.3 ENSP00000276893.5 Q96PU4-1
UHRF2ENST00000468435.6 linkuse as main transcriptn.977G>A non_coding_transcript_exon_variant 6/171 ENSP00000434182.1 Q96PU4-2
UHRF2ENST00000450508.1 linkuse as main transcriptc.308G>A p.Arg103Gln missense_variant 4/43 ENSP00000399217.2 A0A0A0MSQ3
UHRF2ENST00000484159.5 linkuse as main transcriptn.419G>A non_coding_transcript_exon_variant 4/82

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152160
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00000409
AC:
1
AN:
244408
Hom.:
0
AF XY:
0.00000758
AC XY:
1
AN XY:
131998
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:
0.00000898
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1451008
Hom.:
0
Cov.:
30
AF XY:
0.00000971
AC XY:
7
AN XY:
720872
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:
0.0000188
Gnomad4 NFE exome
AF:
0.0000127
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152160
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.0000151

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 GeneticsAug 01, 2022The c.977G>A (p.R326Q) alteration is located in exon 6 (coding exon 6) of the UHRF2 gene. This alteration results from a G to A substitution at nucleotide position 977, causing the arginine (R) at amino acid position 326 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
0.087
BayesDel_addAF
Benign
-0.088
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.041
T;T
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.29
FATHMM_MKL
Benign
0.41
N
LIST_S2
Uncertain
0.90
D;D
M_CAP
Benign
0.049
D
MetaRNN
Benign
0.073
T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
-0.35
N;.
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.11
N;N
REVEL
Benign
0.11
Sift
Benign
0.20
T;T
Sift4G
Benign
0.24
T;D
Polyphen
0.0
B;.
Vest4
0.096
MutPred
0.29
Gain of ubiquitination at K322 (P = 0.0696);.;
MVP
0.36
MPC
0.75
ClinPred
0.20
T
GERP RS
2.3
Varity_R
0.071
gMVP
0.45

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: rs979660065; hg19: chr9-6477625; API