chr19-49983858-G-A

Variant names:

• chr19-49983858-G-A
• rs3786671
• NM_016440.4:c.1218-2845C>T

Variant summary

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

The NM_016440.4(VRK3):​c.1218-2845C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,120 control chromosomes in the GnomAD database, including 2,323 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 0.16 (2323 hom., cov: 32)
• Consequence: VRK3 NM_016440.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880
• Publications: 15 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.323 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.1218-2845C>T		intron	N/A	NP_057524.3
	VRK3	NM_001025778.2		c.1068-2845C>T		intron	N/A	NP_001020949.1
	VRK3	NM_001308420.3		c.1218-1670C>T		intron	N/A	NP_001295349.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VRK3	ENST00000316763.8	TSL:1 MANE Select	c.1218-2845C>T		intron	N/A	ENSP00000324636.2
	VRK3	ENST00000599538.5	TSL:1	c.1218-2845C>T		intron	N/A	ENSP00000469880.1
	VRK3	ENST00000594092.5	TSL:1	c.1218-1670C>T		intron	N/A	ENSP00000472541.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25051 AN: 152002 Hom.: 2319 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.165 AC: 25076 AN: 152120 Hom.: 2323 Cov.: 32 AF XY: 0.164 AC XY: 12182 AN XY: 74348

African (AFR) AF: 0.115 AC: 4776 AN: 41510

American (AMR) AF: 0.140 AC: 2140 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 726 AN: 3468

East Asian (EAS) AF: 0.336 AC: 1736 AN: 5164

South Asian (SAS) AF: 0.133 AC: 641 AN: 4822

European-Finnish (FIN) AF: 0.131 AC: 1383 AN: 10592

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12937 AN: 67964

Other (OTH) AF: 0.174 AC: 369 AN: 2116

Alfa AF: 0.165 Hom.: 790

Bravo AF: 0.165

Asia WGS AF: 0.203 AC: 705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.72
PhyloP100		0.088
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: rs3786671; hg19: chr19-50487115;