14-96855352-C-T

Position:

chr14-96855352-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_003384.3(VRK1):c.705C>T(p.Gly235Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 1,613,562 control chromosomes in the GnomAD database, including 113,086 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 10083 hom., cov: 32)

Exomes 𝑓: 0.36 ( 103003 hom. )

Consequence

VRK1
NM_003384.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.695

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]

VRK1 links:

VRK1 (HGNC:):

VRK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 14-96855352-C-T is Benign according to our data. Variant chr14-96855352-C-T is described in ClinVar as [Benign]. Clinvar id is 130732.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-96855352-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VRK1	NM_003384.3 linkuse as main transcript	c.705C>T	p.Gly235Gly	synonymous_variant	8/13	ENST00000216639.8	NP_003375.1	Q99986

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VRK1	ENST00000216639.8 linkuse as main transcript	c.705C>T	p.Gly235Gly	synonymous_variant	8/13	1	NM_003384.3	ENSP00000216639.3		Q99986

Frequencies

GnomAD3 genomes

AF:

0.336

AC:

51085

AN:

151846

Hom.:

10067

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.374

Gnomad AMR

AF:

0.457

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.841

Gnomad SAS

AF:

0.332

Gnomad FIN

AF:

0.392

Gnomad MID

AF:

0.344

Gnomad NFE

AF:

0.355

Gnomad OTH

AF:

0.356

GnomAD3 exomes

AF:

0.401

AC:

100798

AN:

251282

Hom.:

23093

AF XY:

0.394

AC XY:

53471

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.170

Gnomad AMR exome

AF:

0.503

Gnomad ASJ exome

AF:

0.408

Gnomad EAS exome

AF:

0.855

Gnomad SAS exome

AF:

0.319

Gnomad FIN exome

AF:

0.389

Gnomad NFE exome

AF:

0.354

Gnomad OTH exome

AF:

0.397

GnomAD4 exome

AF:

0.364

AC:

531580

AN:

1461598

Hom.:

103003

Cov.:

AF XY:

0.362

AC XY:

263512

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.164

Gnomad4 AMR exome

AF:

0.499

Gnomad4 ASJ exome

AF:

0.407

Gnomad4 EAS exome

AF:

0.833

Gnomad4 SAS exome

AF:

0.319

Gnomad4 FIN exome

AF:

0.393

Gnomad4 NFE exome

AF:

0.348

Gnomad4 OTH exome

AF:

0.371

GnomAD4 genome

AF:

0.336

AC:

51115

AN:

151964

Hom.:

10083

Cov.:

AF XY:

0.341

AC XY:

25333

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.177

Gnomad4 AMR

AF:

0.457

Gnomad4 ASJ

AF:

0.395

Gnomad4 EAS

AF:

0.842

Gnomad4 SAS

AF:

0.332

Gnomad4 FIN

AF:

0.392

Gnomad4 NFE

AF:

0.355

Gnomad4 OTH

AF:

0.361

Alfa

AF:

0.365

Hom.:

25869

Bravo

AF:

0.338

Asia WGS

AF:

0.517

AC:

1795

AN:

3478

EpiCase

AF:

0.355

EpiControl

AF:

0.360

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Pontocerebellar hypoplasia type 1A

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

not specified

Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 16, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Congenital pontocerebellar hypoplasia type 1

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.57

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.57

Position offset: -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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over