Variant 10-94683950-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_000772.3(CYP2C18):c.131A>T(p.Gln44Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000048 in 1,457,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CYP2C18
NM_000772.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.63

Variant links:

Genes affected

CYP2C18 (HGNC:2620): (cytochrome P450 family 2 subfamily C member 18) 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 but its specific substrate has not yet been determined. The gene is located within a cluster of cytochrome P450 genes on chromosome 10q24. An additional gene, CYP2C17, was once thought to exist; however, CYP2C17 is now considered an artefact based on a chimera of CYP2C18 and CYP2C19. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CYP2C18 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.883

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP2C18	NM_000772.3 linkuse as main transcript	c.131A>T	p.Gln44Leu	missense_variant	1/9	ENST00000285979.11	NP_000763.1
CYP2C18	NM_001128925.2 linkuse as main transcript	c.131A>T	p.Gln44Leu	missense_variant	1/8		NP_001122397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP2C18	ENST00000285979.11 linkuse as main transcript	c.131A>T	p.Gln44Leu	missense_variant	1/9	1	NM_000772.3	ENSP00000285979	P1	P33260-1
CYP2C18	ENST00000339022.6 linkuse as main transcript	c.131A>T	p.Gln44Leu	missense_variant	1/8	1		ENSP00000341293		P33260-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000282

AC:

AN:

248256

Hom.:

AF XY:

0.0000373

AC XY:

AN XY:

134114

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000383

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1457990

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

725048

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

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

Aug 22, 2023

The c.131A>T (p.Q44L) alteration is located in exon 1 (coding exon 1) of the CYP2C18 gene. This alteration results from a A to T substitution at nucleotide position 131, causing the glutamine (Q) at amino acid position 44 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

T;.

Eigen

Benign

-0.078

Eigen_PC

Benign

-0.086

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.011

MetaRNN

Pathogenic

0.88

D;D

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

0.56

N;N

PROVEAN

Pathogenic

-5.6

D;D

REVEL

Benign

0.25

Sift

Uncertain

0.021

D;D

Sift4G

Uncertain

0.034

D;T

Polyphen

0.28

B;.

Vest4

0.60

MutPred

0.73

Gain of catalytic residue at Q44 (P = 0.0649);Gain of catalytic residue at Q44 (P = 0.0649);

MVP

0.70

MPC

0.018

ClinPred

0.72

GERP RS

2.9

Varity_R

0.26

gMVP

0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over