rs2304113

Variant names:

• chr19-49993229-C-G
• rs2304113
• NM_016440.4:c.871-277G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-49993229-C-G
• chr19-49993229-C-A

Variant summary

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

The NM_016440.4(VRK3):​c.871-277G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,096 control chromosomes in the GnomAD database, including 4,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: 𝑓 0.23 (4433 hom., cov: 32)
• Consequence: VRK3 NM_016440.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.560
• Publications: 8 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 (EAS) allele frequency at 95% confidence interval = 0.322 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VRK3	NM_016440.4	MANE Select	c.871-277G>C		intron	N/A	NP_057524.3
	VRK3	NM_001025778.2		c.721-277G>C		intron	N/A	NP_001020949.1	Q8IV63-3
	VRK3	NM_001308420.3		c.871-277G>C		intron	N/A	NP_001295349.1	Q8IV63-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VRK3	ENST00000316763.8	TSL:1 MANE Select	c.871-277G>C		intron	N/A	ENSP00000324636.2	Q8IV63-1
	VRK3	ENST00000599538.5	TSL:1	c.871-277G>C		intron	N/A	ENSP00000469880.1	Q8IV63-1
	VRK3	ENST00000594092.5	TSL:1	c.871-277G>C		intron	N/A	ENSP00000472541.1	Q8IV63-2

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34881 AN: 151978 Hom.: 4420 Cov.: 32

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.245

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.230 AC: 34930 AN: 152096 Hom.: 4433 Cov.: 32 AF XY: 0.226 AC XY: 16841 AN XY: 74358

African (AFR) AF: 0.325 AC: 13468 AN: 41450

American (AMR) AF: 0.168 AC: 2571 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 751 AN: 3470

East Asian (EAS) AF: 0.335 AC: 1732 AN: 5166

South Asian (SAS) AF: 0.144 AC: 697 AN: 4826

European-Finnish (FIN) AF: 0.132 AC: 1402 AN: 10590

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.198 AC: 13472 AN: 67992

Other (OTH) AF: 0.218 AC: 461 AN: 2114

Alfa AF: 0.128 Hom.: 228

Bravo AF: 0.238

Asia WGS AF: 0.217 AC: 754 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	10
DANN	Benign	0.74
PhyloP100		0.56
PromoterAI		-0.013	Neutral
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: rs2304113; hg19: chr19-50496486;