Genetic Variant NM_000783.4:c.488G>T (chr10-93074852-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000783.4(CYP26A1):c.488G>T(p.Ser163Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,098 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S163N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CYP26A1
NM_000783.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.82

Publications

0 publications found

Variant links:

Genes affected

CYP26A1 (HGNC:2603): (cytochrome P450 family 26 subfamily A 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 endoplasmic reticulum protein acts on retinoids, including all-trans-retinoic acid (RA), with both 4-hydroxylation and 18-hydroxylation activities. This enzyme regulates the cellular level of retinoic acid which is involved in regulation of gene expression in both embryonic and adult tissues. Two alternatively spliced transcript variants of this gene, which encode the distinct isoforms, have been reported. [provided by RefSeq, Jul 2008]

CYP26A1 links:

ENSG00000285846 (HGNC:):

ENSG00000285846 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21948773).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000783.4. 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
	CYP26A1	NM_000783.4	MANE Select	c.488G>T	p.Ser163Ile	missense	Exon 3 of 7	NP_000774.2
	CYP26A1	NM_057157.2		c.281G>T	p.Ser94Ile	missense	Exon 3 of 7	NP_476498.1	O43174-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYP26A1	ENST00000224356.5	TSL:1 MANE Select	c.488G>T	p.Ser163Ile	missense	Exon 3 of 7	ENSP00000224356.4	O43174-1
CYP26A1	ENST00000371531.5	TSL:2	c.281G>T	p.Ser94Ile	missense	Exon 3 of 7	ENSP00000360586.1	O43174-2
CYP26A1	ENST00000622925.1	TSL:2	n.345G>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000807

AC:

AN:

247934

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460098

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726412

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51756

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111914

Other (OTH)

AF:

0.00

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.10

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.77

M_CAP

Benign

0.022

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

2.8

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.7

REVEL

Benign

0.11

Sift

Benign

0.22

Sift4G

Benign

0.49

Polyphen

0.0

Vest4

0.44

MutPred

0.47

Loss of disorder (P = 0.025)

MVP

0.79

MPC

0.24

ClinPred

0.18

GERP RS

3.1

Varity_R

0.22

gMVP

0.54

Mutation Taster

=98/2

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

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