rs193921078
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_173517.6(VKORC1L1):c.493G>A(p.Glu165Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
VKORC1L1
NM_173517.6 missense
NM_173517.6 missense
Scores
7
6
6
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.49
Genes affected
VKORC1L1 (HGNC:21492): (vitamin K epoxide reductase complex subunit 1 like 1) This gene encodes an enzyme important in the vitamin K cycle, which is involved in the carboxylation of glutamate residues present in vitamin K-dependent proteins. The encoded enzyme catalyzes the de-epoxidation of vitamin K 2,3-epoxide. Oxidative stress may upregulate expression of this gene and the encoded protein may protect cells and membrane proteins form oxidative damage. This gene and a related gene (Gene ID: 79001) may have arisen by gene duplication of an ancestral gene. [provided by RefSeq, Oct 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VKORC1L1 | NM_173517.6 | c.493G>A | p.Glu165Lys | missense_variant | 3/3 | ENST00000360768.5 | NP_775788.2 | |
VKORC1L1 | NM_001284342.3 | c.383G>A | p.Arg128Gln | missense_variant | 2/2 | NP_001271271.1 | ||
VKORC1L1 | XM_047419923.1 | c.782G>A | p.Arg261Gln | missense_variant | 4/4 | XP_047275879.1 | ||
VKORC1L1 | XM_011515831.3 | c.406G>A | p.Glu136Lys | missense_variant | 4/4 | XP_011514133.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VKORC1L1 | ENST00000360768.5 | c.493G>A | p.Glu165Lys | missense_variant | 3/3 | 1 | NM_173517.6 | ENSP00000353998 | P1 | |
VKORC1L1 | ENST00000648187.1 | c.634G>A | p.Glu212Lys | missense_variant | 3/3 | ENSP00000497458 | ||||
VKORC1L1 | ENST00000434382.2 | c.383G>A | p.Arg128Gln | missense_variant | 2/2 | 2 | ENSP00000403077 | |||
VKORC1L1 | ENST00000648179.1 | c.493G>A | p.Glu165Lys | missense_variant | 3/3 | ENSP00000497394 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251396Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135876
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461880Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727240
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GnomAD4 genome Cov.: 32
GnomAD4 genome
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32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
.;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Benign
.;L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
.;.;N
REVEL
Uncertain
Sift
Benign
.;.;T
Sift4G
Benign
.;.;T
Polyphen
1.0
.;D;D
Vest4
0.47
MutPred
0.40
.;Gain of MoRF binding (P = 5e-04);Gain of MoRF binding (P = 5e-04);
MVP
0.50
MPC
1.3
ClinPred
D
GERP RS
Varity_R
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at