rs245111

Variant names:

• chr19-50025640-C-T
• rs245111
• ENST00000599538.5:c.-359G>A

Variant summary

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

The ENST00000599538.5(VRK3):​c.-359G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 151,846 control chromosomes in the GnomAD database, including 23,488 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 0.53 (23486 hom., cov: 31)
  • Exomes 𝑓: 0.43 (2 hom.)
• Consequence: VRK3 ENST00000599538.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.53
• Publications: 13 publications found

Genes affected

VRK3 (HGNC:18996): (VRK serine/threonine kinase 3) This gene encodes a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases. In both human and mouse, this gene has substitutions at several residues within the ATP binding motifs that in other kinases have been shown to be required for catalysis. In vitro assays indicate the protein lacks phosphorylation activity. The protein, however, likely retains its substrate binding capability. This gene is widely expressed in human tissues and its protein localizes to the nucleus. Alternative splicing results in multiple transcripts encoding different isoforms. [provided by RefSeq, Jul 2008]

ZNF473 (HGNC:23239): (zinc finger protein 473) This gene encodes a member of the Krueppel C2H2-type zinc-finger family of proteins. The encoded protein, a component of the U7 snRNP complex, plays a role in histone 3'-end pre-mRNA processing and may be required for cell cycle progression to S phase. Expression level and methylation status of this gene may be correlated with bone mineral density. [provided by RefSeq, Jul 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000599538.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VRK3	ENST00000599538.5	TSL:1	c.-359G>A		5_prime_UTR	Exon 1 of 15	ENSP00000469880.1
	VRK3	ENST00000596445.5	TSL:5	c.-65+28G>A		intron	N/A	ENSP00000469092.1
	ZNF473	ENST00000391821.6	TSL:1	c.-552C>T		upstream_gene	N/A	ENSP00000375697.1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80457 AN: 151700 Hom.: 23440 Cov.: 31

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.544

GnomAD4 exome AF: 0.429 AC: 12 AN: 28 Hom.: 2 Cov.: 0 AF XY: 0.409 AC XY: 9 AN XY: 22

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.571 AC: 8 AN: 14

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AF: 0.200 AC: 2 AN: 10

GnomAD4 genome AF: 0.531 AC: 80556 AN: 151818 Hom.: 23486 Cov.: 31 AF XY: 0.527 AC XY: 39111 AN XY: 74172

African (AFR) AF: 0.759 AC: 31438 AN: 41418

American (AMR) AF: 0.474 AC: 7234 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.522 AC: 1811 AN: 3468

East Asian (EAS) AF: 0.796 AC: 4066 AN: 5108

South Asian (SAS) AF: 0.581 AC: 2798 AN: 4816

European-Finnish (FIN) AF: 0.327 AC: 3438 AN: 10522

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27940 AN: 67922

Other (OTH) AF: 0.543 AC: 1145 AN: 2110

Alfa AF: 0.447 Hom.: 13897

Bravo AF: 0.556

Asia WGS AF: 0.702 AC: 2443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.11
DANN	Benign	0.82
PhyloP100		-3.5
PromoterAI		-0.0086	Neutral
Mutation Taster		=298/2	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs245111; hg19: chr19-50528897;