19-4910973-C-A

Variant names:

• chr19-4910973-C-A
• rs763928060
• NM_001048201.3:c.88C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001048201.3(UHRF1):​c.88C>A​(p.Arg30Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UHRF1 NM_001048201.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293
• Publications: 1 publications found

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]

ARRDC5 (HGNC:31407): (arrestin domain containing 5) Predicted to enable ubiquitin ligase-substrate adaptor activity and ubiquitin protein ligase binding activity. Predicted to be involved in protein transport. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=-0.293 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UHRF1	NM_001048201.3	MANE Select	c.88C>A	p.Arg30Arg	synonymous	Exon 2 of 17	NP_001041666.1	Q96T88-1
	UHRF1	NM_013282.5		c.127C>A	p.Arg43Arg	synonymous	Exon 1 of 16	NP_037414.3
	UHRF1	NM_001290050.2		c.88C>A	p.Arg30Arg	synonymous	Exon 2 of 17	NP_001276979.1	Q96T88-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UHRF1	ENST00000650932.1	MANE Select	c.88C>A	p.Arg30Arg	synonymous	Exon 2 of 17	ENSP00000498698.1	Q96T88-1
	UHRF1	ENST00000620565.4	TSL:1	c.280C>A	p.Arg94Arg	synonymous	Exon 2 of 17	ENSP00000478171.1	A0A087WTW0
	UHRF1	ENST00000622802.4	TSL:1	c.127C>A	p.Arg43Arg	synonymous	Exon 1 of 16	ENSP00000479617.1	A0A087WVR3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	7.5
DANN	Benign	0.87
PhyloP100		-0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs763928060; hg19: chr19-4910985;