VKORC1 p.Arg12Arg

Variant names:

• chr16-31094693-G-G
• NM_024006.6:c.

Your query was ambiguous. Multiple possible variants found:

• chr16-31094694--
• chr16-31094694-C-A
• chr16-31094694-C-G
• chr16-31094694-C-T
• chr16-31094696-G-T
• chr16-31094694-CCG-TCT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024006.6(VKORC1):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VKORC1 NM_024006.6 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.38
• Publications: 0 publications found

Genes affected

VKORC1 (HGNC:23663): (vitamin K epoxide reductase complex subunit 1) This gene encodes the catalytic subunit of the vitamin K epoxide reductase complex, which is responsible for the reduction of inactive vitamin K 2,3-epoxide to active vitamin K in the endoplasmic reticulum membrane. Vitamin K is a required co-factor for carboxylation of glutamic acid residues by vitamin K-dependent gamma-carboxylase in blood-clotting enzymes. Allelic variation in this gene is associated with vitamin k-dependent clotting factors combined deficiency of 2, and increased resistance or sensitivity to warfarin, an inhibitor of vitamin K epoxide reductase. Pseudogenes of this gene are located on chromosomes 1 and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

VKORC1 Gene-Disease associations (from GenCC):

• vitamin K-dependent clotting factors, combined deficiency of, type 2

  Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• vitamin K-dependent clotting factors, combined deficiency of, type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000255439 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024006.6. 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
	VKORC1	NM_024006.6	MANE Select	c.		exon_region	Exon 1 of 3	NP_076869.1	Q9BQB6-1
	VKORC1	NM_001311311.2		c.		exon_region	Exon 1 of 4	NP_001298240.1
	VKORC1	NM_206824.3		c.		exon_region	Exon 1 of 2	NP_996560.1	Q9BQB6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VKORC1	ENST00000394975.3	TSL:1 MANE Select	c.		exon_region	Exon 1 of 3	ENSP00000378426.2	Q9BQB6-1
	ENSG00000255439	ENST00000529564.1	TSL:4	c.		exon_region	Exon 1 of 5	ENSP00000431371.1	E9PLN8
	VKORC1	ENST00000319788.11	TSL:1	c.		exon_region	Exon 1 of 4	ENSP00000326135.7	Q9BQB6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-31106014;