rs1555360117

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003384.3(VRK1):​c.184G>A​(p.Val62Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000707 in 1,414,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

VRK1
NM_003384.3 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 5.57
Variant links:
Genes affected
VRK1 (HGNC:12718): (VRK serine/threonine kinase 1) This gene encodes a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases. This gene is widely expressed in human tissues and has increased expression in actively dividing cells, such as those in testis, thymus, fetal liver, and carcinomas. Its protein localizes to the nucleus and has been shown to promote the stability and nuclear accumulation of a transcriptionally active p53 molecule and, in vitro, to phosphorylate Thr18 of p53 and reduce p53 ubiquitination. This gene, therefore, may regulate cell proliferation. This protein also phosphorylates histone, casein, and the transcription factors ATF2 (activating transcription factor 2) and c-JUN. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32972306).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
VRK1NM_003384.3 linkuse as main transcriptc.184G>A p.Val62Ile missense_variant 3/13 ENST00000216639.8 NP_003375.1 Q99986

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
VRK1ENST00000216639.8 linkuse as main transcriptc.184G>A p.Val62Ile missense_variant 3/131 NM_003384.3 ENSP00000216639.3 Q99986

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.07e-7
AC:
1
AN:
1414284
Hom.:
0
Cov.:
29
AF XY:
0.00000142
AC XY:
1
AN XY:
702142
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoMay 23, 2016- -
Pontocerebellar hypoplasia type 1A Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 02, 2021This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 62 of the VRK1 protein (p.Val62Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with VRK1-related conditions. ClinVar contains an entry for this variant (Variation ID: 437263). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.093
BayesDel_addAF
Uncertain
0.036
T
BayesDel_noAF
Benign
-0.19
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
T
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.33
T
MetaSVM
Benign
-0.71
T
MutationAssessor
Uncertain
2.0
M
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-0.81
N
REVEL
Benign
0.17
Sift
Uncertain
0.026
D
Sift4G
Benign
0.15
T
Polyphen
0.80
P
Vest4
0.29
MutPred
0.36
Gain of catalytic residue at S61 (P = 0);
MVP
0.64
MPC
0.25
ClinPred
0.59
D
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.31
gMVP
0.32

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs1555360117; hg19: chr14-97304122; API