9-6477636-G-C
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_152896.3(UHRF2):āc.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
NM_152896.3 missense
Scores
2
8
9
Clinical Significance
Conservation
PhyloP100: 8.01
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]
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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
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
UHRF2 | ENST00000276893.10 | c.988G>C | p.Glu330Gln | missense_variant | 6/16 | 1 | NM_152896.3 | ENSP00000276893.5 | ||
UHRF2 | ENST00000468435.6 | n.988G>C | non_coding_transcript_exon_variant | 6/17 | 1 | ENSP00000434182.1 | ||||
UHRF2 | ENST00000450508.1 | c.319G>C | p.Glu107Gln | missense_variant | 4/4 | 3 | ENSP00000399217.2 | |||
UHRF2 | ENST00000484159.5 | n.430G>C | non_coding_transcript_exon_variant | 4/8 | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152194Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249404Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134752
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GnomAD4 exome AF: 0.00000891 AC: 13AN: 1459680Hom.: 0 Cov.: 30 AF XY: 0.00000964 AC XY: 7AN XY: 726046
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74352
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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 | Jun 30, 2024 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;D
Sift4G
Benign
T;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at