9-6455048-T-C

Position:

• chr9-6455048-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UHRF2	NM_152896.3	c.645-5525T>C		intron_variant		ENST00000276893.10	NP_690856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UHRF2	ENST00000276893.10	c.645-5525T>C		intron_variant		1	NM_152896.3	ENSP00000276893.5

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

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.579

Gnomad4 FIN AF: 0.605

Gnomad4 NFE AF: 0.614

Gnomad4 OTH AF: 0.558

Alfa AF: 0.601 Hom.: 57822

Bravo AF: 0.541

Asia WGS AF: 0.596 AC: 2070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.67

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

Other links and lift over

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