rs16981592

Variant names:

• chr19-49977452-T-C
• rs16981592
• NM_016440.4:c.*12-668A>G

Variant summary

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

The NM_016440.4(VRK3):​c.*12-668A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0533 in 152,068 control chromosomes in the GnomAD database, including 714 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 0.053 (714 hom., cov: 32)
• Consequence: VRK3 NM_016440.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 3 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016440.4. 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
	VRK3	NM_016440.4	MANE Select	c.*12-668A>G		intron	N/A	NP_057524.3
	VRK3	NM_001025778.2		c.*12-668A>G		intron	N/A	NP_001020949.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VRK3	ENST00000316763.8	TSL:1 MANE Select	c.*12-668A>G		intron	N/A	ENSP00000324636.2
	VRK3	ENST00000599538.5	TSL:1	c.*12-668A>G		intron	N/A	ENSP00000469880.1
	VRK3	ENST00000377011.6	TSL:5	c.*12-668A>G		intron	N/A	ENSP00000366210.1

Frequencies

GnomAD3 genomes AF: 0.0532 AC: 8087 AN: 151950 Hom.: 712 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0200

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.0340

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

GnomAD4 genome AF: 0.0533 AC: 8112 AN: 152068 Hom.: 714 Cov.: 32 AF XY: 0.0510 AC XY: 3791 AN XY: 74342

African (AFR) AF: 0.186 AC: 7703 AN: 41414

American (AMR) AF: 0.0200 AC: 305 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 67996

Other (OTH) AF: 0.0336 AC: 71 AN: 2110

Alfa AF: 0.0299 Hom.: 125

Bravo AF: 0.0613

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.80
DANN	Benign	0.25
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs16981592; hg19: chr19-50480709;