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GeneBe

rs1799853

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM5PP3

The NM_000771.4(CYP2C9):c.430C>A(p.Arg144Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R144C) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

CYP2C9
NM_000771.4 missense

Scores

1
5
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0520
Variant links:
Genes affected
CYP2C9 (HGNC:2623): (cytochrome P450 family 2 subfamily C member 9) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by rifampin. The enzyme is known to metabolize many xenobiotics, including phenytoin, tolbutamide, ibuprofen and S-warfarin. Studies identifying individuals who are poor metabolizers of phenytoin and tolbutamide suggest that this gene is polymorphic. The gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr10-94942290-C-T is described in Lovd as [Pathogenic].
PP3
MetaRNN computational evidence supports a deleterious effect, 0.746

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CYP2C9NM_000771.4 linkuse as main transcriptc.430C>A p.Arg144Ser missense_variant 3/9 ENST00000260682.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYP2C9ENST00000260682.8 linkuse as main transcriptc.430C>A p.Arg144Ser missense_variant 3/91 NM_000771.4 P1P11712-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.53
BayesDel_addAF
Uncertain
0.029
T
BayesDel_noAF
Benign
-0.20
Cadd
Benign
18
Dann
Uncertain
1.0
Eigen
Benign
-0.10
Eigen_PC
Benign
-0.32
FATHMM_MKL
Benign
0.051
N
LIST_S2
Benign
0.43
T;T
M_CAP
Benign
0.037
D
MetaRNN
Pathogenic
0.75
D;D
MetaSVM
Uncertain
-0.26
T
MutationAssessor
Uncertain
2.8
M;M
MutationTaster
Benign
0.66
D
PrimateAI
Benign
0.31
T
Polyphen
1.0
.;D
Vest4
0.53
MutPred
0.57
Gain of phosphorylation at R144 (P = 0.0367);Gain of phosphorylation at R144 (P = 0.0367);
MVP
0.81
MPC
0.054
ClinPred
0.97
D
GERP RS
1.4
Varity_R
0.93
gMVP
0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-96702047; API