Variant 9-6413513-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_152896.3(UHRF2):c.23T>C(p.Ile8Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000021 in 1,429,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

UHRF2
NM_152896.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.14

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]

UHRF2 links:

UHRF2 (HGNC:):

UHRF2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.844

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UHRF2	NM_152896.3 linkuse as main transcript	c.23T>C	p.Ile8Thr	missense_variant	1/16	ENST00000276893.10	NP_690856.1	Q96PU4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UHRF2	ENST00000276893.10 linkuse as main transcript	c.23T>C	p.Ile8Thr	missense_variant	1/16	1	NM_152896.3	ENSP00000276893.5	Q96PU4-1
UHRF2	ENST00000468435.6 linkuse as main transcript	n.23T>C		non_coding_transcript_exon_variant	1/17	1		ENSP00000434182.1	Q96PU4-2
UHRF2	ENST00000381373.3 linkuse as main transcript	c.23T>C	p.Ile8Thr	missense_variant	1/3	3		ENSP00000370778.3	B1AL33
UHRF2	ENST00000469298.5 linkuse as main transcript	n.194T>C		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000448

AC:

AN:

223092

Hom.:

AF XY:

0.00

AC XY:

AN XY:

121838

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:

0.00000978

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000210

AC:

AN:

1429742

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

711322

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:

0.00000273

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Nov 13, 2024

The c.23T>C (p.I8T) alteration is located in exon 1 (coding exon 1) of the UHRF2 gene. This alteration results from a T to C substitution at nucleotide position 23, causing the isoleucine (I) at amino acid position 8 to be replaced by a threonine (T). 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

Pathogenic

0.80

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Uncertain

0.13

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.97

D;D

M_CAP

Pathogenic

0.73

MetaRNN

Pathogenic

0.84

D;D

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

2.0

M;.

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-2.1

N;D

REVEL

Uncertain

0.63

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.97

D;.

Vest4

0.72

MutPred

0.68

Loss of stability (P = 0.0044);Loss of stability (P = 0.0044);

MVP

0.89

MPC

1.1

ClinPred

0.77

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.32

gMVP

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over