19-50020969-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0630
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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
VRK3NM_016440.4 linkc.-64-322T>C intron_variant Intron 1 of 14 ENST00000316763.8 NP_057524.3 Q8IV63-1A0A024QZI4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VRK3ENST00000316763.8 linkc.-64-322T>C intron_variant Intron 1 of 14 1 NM_016440.4 ENSP00000324636.2 Q8IV63-1

Frequencies

GnomAD3 genomes
AF:
0.499
AC:
75718
AN:
151836
Hom.:
19558
Cov.:
31
show subpopulations
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
show subpopulations
Gnomad4 AFR
AF:
0.554
Gnomad4 AMR
AF:
0.566
Gnomad4 ASJ
AF:
0.544
Gnomad4 EAS
AF:
0.811
Gnomad4 SAS
AF:
0.576
Gnomad4 FIN
AF:
0.296
Gnomad4 NFE
AF:
0.450
Gnomad4 OTH
AF:
0.521
Alfa
AF:
0.471
Hom.:
22504
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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs734910; hg19: chr19-50524226; API