chr10-95064897-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000770.3(CYP2C8):c.545T>C(p.Val182Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
CYP2C8
NM_000770.3 missense
NM_000770.3 missense
Scores
1
7
5
Clinical Significance
Conservation
PhyloP100: 8.31
Genes affected
CYP2C8 (HGNC:2622): (cytochrome P450 family 2 subfamily C member 8) 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 phenobarbital. The enzyme is known to metabolize many xenobiotics, including the anticonvulsive drug mephenytoin, benzo(a)pyrene, 7-ethyoxycoumarin, and the anti-cancer drug taxol. This gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. Several transcript variants encoding a few different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]
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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 | UniProt |
---|---|---|---|---|---|---|---|
CYP2C8 | NM_000770.3 | c.545T>C | p.Val182Ala | missense_variant | 4/9 | ENST00000371270.6 | |
CYP2C8 | NM_001198853.1 | c.335T>C | p.Val112Ala | missense_variant | 4/9 | ||
CYP2C8 | NM_001198855.1 | c.335T>C | p.Val112Ala | missense_variant | 5/10 | ||
CYP2C8 | NM_001198854.1 | c.239T>C | p.Val80Ala | missense_variant | 3/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP2C8 | ENST00000371270.6 | c.545T>C | p.Val182Ala | missense_variant | 4/9 | 1 | NM_000770.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 07, 2024 | The c.545T>C (p.V182A) alteration is located in exon 4 (coding exon 4) of the CYP2C8 gene. This alteration results from a T to C substitution at nucleotide position 545, causing the valine (V) at amino acid position 182 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
Sift4G
Uncertain
D;D;D;D;D
Polyphen
0.95
.;.;.;P;.
Vest4
MutPred
0.64
.;.;.;Loss of methylation at K185 (P = 0.1325);.;
MVP
MPC
0.11
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.