Genetic Variant ENST00000319788.11:c.294G>T (chr16-31092854-C-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The ENST00000319788.11(VKORC1):c.294G>T(p.Ser98Ser) variant causes a 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S98S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

VKORC1
ENST00000319788.11 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.454

Publications

0 publications found

Variant links:

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

VKORC1 links:

ENSG00000255439 (HGNC:):

ENSG00000255439 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 (BayesDel_noAF=-0.9).

BP7

Synonymous conserved (PhyloP=-0.454 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VKORC1	NM_024006.6 link	c.283+458G>T		intron_variant	Intron 2 of 2	ENST00000394975.3	NP_076869.1	Q9BQB6-1A0A0S2Z6I4
VKORC1	NM_001311311.2 link	c.296G>T	p.Arg99Leu	missense_variant	Exon 3 of 4		NP_001298240.1	Q9BQB6
VKORC1	NM_206824.3 link	c.174-1512G>T		intron_variant	Intron 1 of 1		NP_996560.1	Q9BQB6-3A0A0S2Z5X7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VKORC1	ENST00000394975.3 link	c.283+458G>T		intron_variant	Intron 2 of 2	1	NM_024006.6	ENSP00000378426.2		Q9BQB6-1
ENSG00000255439	ENST00000529564.1 link	c.283+458G>T		intron_variant	Intron 2 of 4	4		ENSP00000431371.1		E9PLN8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000120

AC:

AN:

82994

AF XY:

0.0000214

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000313

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

861560

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

427036

African (AFR)

AF:

0.00

AC:

AN:

17324

American (AMR)

AF:

0.00

AC:

AN:

17130

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12248

East Asian (EAS)

AF:

0.00

AC:

AN:

10088

South Asian (SAS)

AF:

0.00

AC:

AN:

64508

European-Finnish (FIN)

AF:

0.00

AC:

AN:

11556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3688

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

693320

Other (OTH)

AF:

0.00

AC:

AN:

31698

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.35

(source)

DANN

Benign

0.68

PhyloP100

-0.45

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over