19-50020969-A-G

Variant names:

• chr19-50020969-A-G
• rs734910
• NM_016440.4:c.-64-322T>C

Variant summary

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

The NM_016440.4(VRK3):​c.-64-322T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 151,954 control chromosomes in the GnomAD database, including 19,599 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 0.50 (19599 hom., cov: 31)
• Consequence: VRK3 NM_016440.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VRK3	NM_016440.4	c.-64-322T>C		intron_variant	Intron 1 of 14	ENST00000316763.8	NP_057524.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VRK3	ENST00000316763.8	c.-64-322T>C		intron_variant	Intron 1 of 14	1	NM_016440.4	ENSP00000324636.2

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75718 AN: 151836 Hom.: 19558 Cov.: 31

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.499 AC: 75814 AN: 151954 Hom.: 19599 Cov.: 31 AF XY: 0.498 AC XY: 36977 AN XY: 74278

African (AFR) AF: 0.554 AC: 22929 AN: 41384

American (AMR) AF: 0.566 AC: 8655 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1886 AN: 3466

East Asian (EAS) AF: 0.811 AC: 4194 AN: 5170

South Asian (SAS) AF: 0.576 AC: 2774 AN: 4818

European-Finnish (FIN) AF: 0.296 AC: 3128 AN: 10568

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30588 AN: 67944

Other (OTH) AF: 0.521 AC: 1099 AN: 2108

Alfa AF: 0.477 Hom.: 29397

Bravo AF: 0.523

Asia WGS AF: 0.705 AC: 2452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.7
DANN	Benign	0.52
PhyloP100		-0.063
PromoterAI		0.053	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: rs734910; hg19: chr19-50524226;