NM_152896.3:c.1393-513G>C

Variant names:

• chr9-6486308-G-C
• rs16924631
• NM_152896.3:c.1393-513G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152896.3(UHRF2):​c.1393-513G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 152,124 control chromosomes in the GnomAD database, including 2,323 homozygotes. 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: 𝑓 0.17 (2323 hom., cov: 32)
• Consequence: UHRF2 NM_152896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• Publications: 7 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152896.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UHRF2	NM_152896.3	MANE Select	c.1393-513G>C		intron	N/A	NP_690856.1
	UHRF2	NR_046386.2		n.1685-513G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UHRF2	ENST00000276893.10	TSL:1 MANE Select	c.1393-513G>C		intron	N/A	ENSP00000276893.5
	UHRF2	ENST00000468435.7	TSL:1	n.1393-513G>C		intron	N/A	ENSP00000434182.1
	UHRF2	ENST00000477183.1	TSL:3	n.140-513G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25703 AN: 152006 Hom.: 2327 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.176

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.169 AC: 25706 AN: 152124 Hom.: 2323 Cov.: 32 AF XY: 0.174 AC XY: 12905 AN XY: 74364

African (AFR) AF: 0.161 AC: 6687 AN: 41500

American (AMR) AF: 0.216 AC: 3300 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 508 AN: 3470

East Asian (EAS) AF: 0.274 AC: 1419 AN: 5178

South Asian (SAS) AF: 0.170 AC: 819 AN: 4824

European-Finnish (FIN) AF: 0.199 AC: 2106 AN: 10566

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.152 AC: 10341 AN: 68004

Other (OTH) AF: 0.174 AC: 367 AN: 2104

Alfa AF: 0.166 Hom.: 283

Bravo AF: 0.167

Asia WGS AF: 0.208 AC: 724 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.4
DANN	Benign	0.76
PhyloP100		-0.055
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs16924631; hg19: chr9-6486308;