dbSNP rs770233968: UHRF1:p.Arg282Gly (chr19-4941586-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001048201.3(UHRF1):c.844C>G(p.Arg282Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R282W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

UHRF1
NM_001048201.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.01

Publications

0 publications found

Variant links:

Genes affected

UHRF1 (HGNC:12556): (ubiquitin like with PHD and ring finger domains 1) This gene encodes a member of a subfamily of RING-finger type E3 ubiquitin ligases. The protein binds to specific DNA sequences, and recruits a histone deacetylase to regulate gene expression. Its expression peaks at late G1 phase and continues during G2 and M phases of the cell cycle. It plays a major role in the G1/S transition by regulating topoisomerase IIalpha and retinoblastoma gene expression, and functions in the p53-dependent DNA damage checkpoint. It is regarded as a hub protein for the integration of epigenetic information. This gene is up-regulated in various cancers, and it is therefore considered to be a therapeutic target. Multiple transcript variants encoding different isoforms have been found for this gene. A related pseudogene exists on chromosome 12. [provided by RefSeq, Feb 2014]

UHRF1 Gene-Disease associations (from GenCC):

immunodeficiency-centromeric instability-facial anomalies syndrome
Inheritance: AR Classification: LIMITED Submitted by: G2P

UHRF1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10448435).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001048201.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UHRF1	NM_001048201.3	MANE Select	c.844C>G	p.Arg282Gly	missense	Exon 6 of 17	NP_001041666.1	Q96T88-1
UHRF1	NM_013282.5		c.883C>G	p.Arg295Gly	missense	Exon 5 of 16	NP_037414.3
UHRF1	NM_001290050.2		c.844C>G	p.Arg282Gly	missense	Exon 6 of 17	NP_001276979.1	Q96T88-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UHRF1	ENST00000650932.1	MANE Select	c.844C>G	p.Arg282Gly	missense	Exon 6 of 17	ENSP00000498698.1	Q96T88-1
UHRF1	ENST00000620565.4	TSL:1	c.1036C>G	p.Arg346Gly	missense	Exon 6 of 17	ENSP00000478171.1	A0A087WTW0
UHRF1	ENST00000622802.4	TSL:1	c.883C>G	p.Arg295Gly	missense	Exon 5 of 16	ENSP00000479617.1	A0A087WVR3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000403

AC:

AN:

248018

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000891

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

0.0070

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.30

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.74

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

4.0

PrimateAI

Benign

0.29

Sift4G

Uncertain

0.056

Polyphen

0.14

Vest4

0.29

MutPred

0.38

Gain of catalytic residue at R282 (P = 0.034)

MVP

0.27

ClinPred

0.21

GERP RS

2.3

Varity_R

0.28

gMVP

0.79

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over