rs137853063

Variant names:

• chr14-96876033-C-A
• rs137853063
• NM_003384.3:c.1072C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-96876033-C-A
• chr14-96876033-C-T
• chr14-96876033-C-G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001411053.1(VRK1):​c.1069C>A​(p.Arg357Arg) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VRK1 NM_001411053.1 splice_region, synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00600
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 1A

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, G2P
• microcephaly-complex motor and sensory axonal neuropathy syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• pontocerebellar hypoplasia type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.145).
• BP6: Variant 14-96876033-C-A is Benign according to our data. Variant chr14-96876033-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2811671.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.006 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001411053.1. 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
	VRK1	NM_003384.3	MANE Select	c.1072C>A	p.Arg358Arg	synonymous	Exon 12 of 13	NP_003375.1	Q99986
	VRK1	NM_001411051.1		c.1072C>A	p.Arg358Arg	synonymous	Exon 12 of 14	NP_001397980.1	H0YJF7
	VRK1	NM_001411053.1		c.1069C>A	p.Arg357Arg	splice_region synonymous	Exon 12 of 13	NP_001397982.1	A0A7P0T838

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VRK1	ENST00000216639.8	TSL:1 MANE Select	c.1072C>A	p.Arg358Arg	synonymous	Exon 12 of 13	ENSP00000216639.3	Q99986
	VRK1	ENST00000679462.1		c.1107C>A	p.Ser369Arg	missense	Exon 11 of 12	ENSP00000506011.1	A0A7P0TAA6
	VRK1	ENST00000679770.1		c.1072C>A	p.Arg358Arg	synonymous	Exon 12 of 14	ENSP00000505214.1	A0A7P0Z445

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Pontocerebellar hypoplasia type 1A (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.14
CADD	Benign	7.0
DANN	Benign	0.62
PhyloP100		0.0060
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs137853063; hg19: chr14-97342370;