dbSNP rs2134411007: CYP26C1:p.His110Tyr (chr10-93062133-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_183374.3(CYP26C1):c.328C>T(p.His110Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000717 in 1,395,608 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: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

CYP26C1
NM_183374.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.21

Publications

0 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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.823

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.328C>T	p.His110Tyr	missense	Exon 2 of 6	NP_899230.2	Q6V0L0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYP26C1	ENST00000651965.1	MANE Select	c.328C>T	p.His110Tyr	missense	Exon 2 of 6	ENSP00000498424.1	Q6V0L0
CYP26C1	ENST00000624358.3	TSL:2	n.328C>T		non_coding_transcript_exon	Exon 2 of 6	ENSP00000485098.1	A0A096LNL5
CYP26C1-DT	ENST00000847325.1		n.466G>A		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.17e-7

AC:

AN:

1395608

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

688934

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31908

American (AMR)

AF:

0.00

AC:

AN:

35888

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25178

East Asian (EAS)

AF:

0.00

AC:

AN:

36154

South Asian (SAS)

AF:

0.00

AC:

AN:

79374

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42948

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5690

European-Non Finnish (NFE)

AF:

9.26e-7

AC:

AN:

1080414

Other (OTH)

AF:

0.00

AC:

AN:

58054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.036

MetaRNN

Pathogenic

0.82

MetaSVM

Uncertain

-0.15

MutationAssessor

Pathogenic

3.2

PhyloP100

7.2

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-5.2

REVEL

Uncertain

0.45

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.64

MutPred

0.59

Gain of phosphorylation at H110 (P = 0.0707)

MVP

0.94

MPC

2.0

ClinPred

0.99

GERP RS

5.9

Varity_R

0.91

Mutation Taster

=49/51

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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