9-6455048-T-C

Variant names:

• chr9-6455048-T-C
• rs401733
• NM_152896.3:c.645-5525T>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.645-5525T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 152,074 control chromosomes in the GnomAD database, including 23,658 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 0.55 (23658 hom., cov: 32)
• Consequence: UHRF2 NM_152896.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.609 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UHRF2	NM_152896.3	MANE Select	c.645-5525T>C		intron	N/A	NP_690856.1
	UHRF2	NR_046386.2		n.937-5525T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UHRF2	ENST00000276893.10	TSL:1 MANE Select	c.645-5525T>C		intron	N/A	ENSP00000276893.5
	UHRF2	ENST00000468435.7	TSL:1	n.645-5525T>C		intron	N/A	ENSP00000434182.1
	UHRF2	ENST00000934278.1		c.636-5525T>C		intron	N/A	ENSP00000604337.1

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83540 AN: 151956 Hom.: 23644 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.580

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.550 AC: 83574 AN: 152074 Hom.: 23658 Cov.: 32 AF XY: 0.547 AC XY: 40660 AN XY: 74342

African (AFR) AF: 0.419 AC: 17391 AN: 41496

American (AMR) AF: 0.513 AC: 7844 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2337 AN: 3468

East Asian (EAS) AF: 0.590 AC: 3055 AN: 5174

South Asian (SAS) AF: 0.579 AC: 2784 AN: 4806

European-Finnish (FIN) AF: 0.605 AC: 6398 AN: 10570

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.614 AC: 41758 AN: 67968

Other (OTH) AF: 0.558 AC: 1178 AN: 2110

Alfa AF: 0.594 Hom.: 115853

Bravo AF: 0.541

Asia WGS AF: 0.596 AC: 2070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.67
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

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: rs401733; hg19: chr9-6455048; COSMIC: COSV52791862;