Genetic Variant CYP26C1:p.Pro178Arg (chr10-93062823-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_183374.3(CYP26C1):c.533C>G(p.Pro178Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000898 in 1,570,786 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: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000092 ( 0 hom. )

Consequence

CYP26C1
NM_183374.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.90

Variant links:

Genes affected

CYP26C1 (HGNC:20577): (cytochrome P450 family 26 subfamily C member 1) 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 enzyme is involved in the catabolism of all-trans- and 9-cis-retinoic acid, and thus contributes to the regulation of retinoic acid levels in cells and tissues. This gene is adjacent to a related gene on chromosome 10q23.33. [provided by RefSeq, Jul 2008]

CYP26C1 links:

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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 rank	MANE	Protein	UniProt
CYP26C1	NM_183374.3 link	c.533C>G	p.Pro178Arg	missense_variant	Exon 3 of 6	ENST00000651965.1	NP_899230.2	Q6V0L0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP26C1	ENST00000651965.1 link	c.533C>G	p.Pro178Arg	missense_variant	Exon 3 of 6		NM_183374.3	ENSP00000498424.1		Q6V0L0
CYP26C1	ENST00000624358.3 link	n.533C>G		non_coding_transcript_exon_variant	Exon 3 of 6	2		ENSP00000485098.1		A0A096LNL5

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000941

AC:

AN:

180604

Hom.:

AF XY:

0.0000800

AC XY:

AN XY:

100060

show subpopulations

Gnomad AFR exome

AF:

0.000199

Gnomad AMR exome

AF:

0.000205

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000136

Gnomad SAS exome

AF:

0.0000757

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000656

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000923

AC:

131

AN:

1418604

Hom.:

Cov.:

AF XY:

0.0000910

AC XY:

AN XY:

703544

show subpopulations

Gnomad4 AFR exome

AF:

0.000123

Gnomad4 AMR exome

AF:

0.000174

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000157

Gnomad4 SAS exome

AF:

0.0000845

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000939

Gnomad4 OTH exome

AF:

0.0000677

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000106

ExAC

AF:

0.0000850

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.71

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.53

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.3

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-4.4

REVEL

Uncertain

0.39

Sift

Benign

0.32

Sift4G

Benign

0.069

Polyphen

1.0

Vest4

0.45

MutPred

0.50

Gain of MoRF binding (P = 4e-04);

MVP

0.92

MPC

1.9

ClinPred

0.72

GERP RS

5.4

Varity_R

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over