10-95045855-G-C

Variant names:

• chr10-95045855-G-C
• rs768402831
• NM_000770.3:c.916C>G

Variant summary

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

The NM_000770.3(CYP2C8):​c.916C>G​(p.Leu306Val) variant causes a missense 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L306M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYP2C8 NM_000770.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394
• Publications: 0 publications found

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]

ACMG classification

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

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP2C8	NM_000770.3	c.916C>G	p.Leu306Val	missense_variant	Exon 6 of 9	ENST00000371270.6	NP_000761.3
CYP2C8	NM_001198853.1	c.706C>G	p.Leu236Val	missense_variant	Exon 6 of 9		NP_001185782.1
CYP2C8	NM_001198855.1	c.706C>G	p.Leu236Val	missense_variant	Exon 7 of 10		NP_001185784.1
CYP2C8	NM_001198854.1	c.610C>G	p.Leu204Val	missense_variant	Exon 5 of 8		NP_001185783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP2C8	ENST00000371270.6	c.916C>G	p.Leu306Val	missense_variant	Exon 6 of 9	1	NM_000770.3	ENSP00000360317.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	.;.;.;T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.40	N
LIST_S2	Uncertain	0.90	.;D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.54	D;D;D;D;D
MetaSVM	Benign	-0.45	T
MutationAssessor	Pathogenic	3.4	.;.;.;M;.
PhyloP100		-0.39
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-2.5	.;N;.;N;.
REVEL	Uncertain	0.55
Sift	Uncertain	0.021	.;D;.;D;.
Sift4G	Uncertain	0.015	D;D;D;D;D
Polyphen		0.72	.;.;.;P;.
Vest4		0.35
MutPred		0.82		.;.;.;Loss of stability (P = 0.0926);.;
MVP		0.56
MPC		0.10
ClinPred		0.93	D
GERP RS		2.5
Varity_R		0.45
gMVP		0.070
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs768402831; hg19: chr10-96805612;