Variant 10-93062160-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PM5BP4

The NM_183374.3(CYP26C1):c.355C>G(p.Gln119Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000576 in 1,388,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q119P) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000058 ( 0 hom. )

Consequence

CYP26C1
NM_183374.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.38

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr10-93062161-A-C is described in Lovd as [Likely_pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.3242121).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP26C1	NM_183374.3 linkuse as main transcript	c.355C>G	p.Gln119Glu	missense_variant	2/6	ENST00000651965.1	NP_899230.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP26C1	ENST00000651965.1 linkuse as main transcript	c.355C>G	p.Gln119Glu	missense_variant	2/6		NM_183374.3	ENSP00000498424	P1
CYP26C1	ENST00000624358.3 linkuse as main transcript	c.355C>G	p.Gln119Glu	missense_variant, NMD_transcript_variant	2/6	2		ENSP00000485098

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000290

AC:

AN:

137776

Hom.:

AF XY:

0.0000270

AC XY:

AN XY:

74140

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000122

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000192

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000576

AC:

AN:

1388186

Hom.:

Cov.:

AF XY:

0.00000584

AC XY:

AN XY:

685128

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000140

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000185

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000125

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

Apr 01, 2024

The c.355C>G (p.Q119E) alteration is located in exon 2 (coding exon 2) of the CYP26C1 gene. This alteration results from a C to G substitution at nucleotide position 355, causing the glutamine (Q) at amino acid position 119 to be replaced by a glutamic acid (E). 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

0.094

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.099

Eigen

Benign

0.0041

Eigen_PC

Benign

0.11

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.73

M_CAP

Benign

0.021

MetaRNN

Benign

0.32

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.4

REVEL

Benign

0.11

Sift

Benign

0.49

Sift4G

Benign

0.34

Polyphen

0.63

Vest4

0.41

MutPred

0.42

Loss of MoRF binding (P = 0.0548);

MVP

0.89

MPC

0.99

ClinPred

0.22

GERP RS

3.7

Varity_R

0.40

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