19-4941544-G-T

Variant names:

• chr19-4941544-G-T
• rs1172511762
• NM_001048201.3:c.802G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001048201.3(UHRF1):​c.802G>T​(p.Asp268Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UHRF1 NM_001048201.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.54

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UHRF1	NM_001048201.3	c.802G>T	p.Asp268Tyr	missense_variant	Exon 6 of 17	ENST00000650932.1	NP_001041666.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UHRF1	ENST00000650932.1	c.802G>T	p.Asp268Tyr	missense_variant	Exon 6 of 17		NM_001048201.3	ENSP00000498698.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461072 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726770

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.50	D;T;D;D;.;D
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.41
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.94	.;D;D;.;D;.
MetaRNN	Uncertain	0.62	D;D;D;D;D;D
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.8	M;.;M;M;.;M
PrimateAI	Benign	0.35	T
Sift4G	Uncertain	0.0050	D;D;D;D;D;D
Polyphen		1.0	D;.;D;D;.;D
Vest4		0.72
MutPred		0.54		Loss of sheet (P = 0.1907);.;Loss of sheet (P = 0.1907);Loss of sheet (P = 0.1907);.;Loss of sheet (P = 0.1907);
MVP		0.20
ClinPred		0.89	D
GERP RS		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.083
gMVP		0.93

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: rs1172511762; hg19: chr19-4941556;