dbSNP rs144906308: CYP26C1:p.Leu28Met (chr10-93061345-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_183374.3(CYP26C1):c.82C>A(p.Leu28Met) 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 benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L28L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CYP26C1
NM_183374.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.247

Publications

2 publications found

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:

CYP26C1-DT (HGNC:55836): (CYP26C1 divergent transcript)

CYP26C1-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36131144).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183374.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP26C1	NM_183374.3	MANE Select	c.82C>A	p.Leu28Met	missense	Exon 1 of 6	NP_899230.2	Q6V0L0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYP26C1	ENST00000651965.1	MANE Select	c.82C>A	p.Leu28Met	missense	Exon 1 of 6	ENSP00000498424.1	Q6V0L0
CYP26C1	ENST00000624358.3	TSL:2	n.82C>A		non_coding_transcript_exon	Exon 1 of 6	ENSP00000485098.1	A0A096LNL5
CYP26C1-DT	ENST00000847325.1		n.532+722G>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1435576

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

711586

African (AFR)

AF:

0.00

AC:

AN:

33134

American (AMR)

AF:

0.00

AC:

AN:

41270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25582

East Asian (EAS)

AF:

0.00

AC:

AN:

38492

South Asian (SAS)

AF:

0.00

AC:

AN:

82194

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50210

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5648

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1099666

Other (OTH)

AF:

0.00

AC:

AN:

59380

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Benign

-0.079

Eigen_PC

Benign

-0.068

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.77

M_CAP

Benign

0.032

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.47

MutationAssessor

Uncertain

2.2

PhyloP100

0.25

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.81

REVEL

Benign

0.22

Sift

Benign

0.087

Sift4G

Uncertain

0.042

Polyphen

0.97

Vest4

0.42

MutPred

0.49

Gain of MoRF binding (P = 0.0713)

MVP

0.82

MPC

0.17

ClinPred

0.89

GERP RS

3.2

Varity_R

0.16

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over