NM_000783.4:c.97G>T

Variant names:

• chr10-93074031-G-T
• rs1293795438
• NM_000783.4:c.97G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000783.4(CYP26A1):​c.97G>T​(p.Val33Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CYP26A1 NM_000783.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45

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]

ENSG00000285846 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12004861).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP26A1	NM_000783.4	c.97G>T	p.Val33Leu	missense_variant	Exon 1 of 7	ENST00000224356.5	NP_000774.2
CYP26A1	NM_057157.2	c.-19+197G>T		intron_variant	Intron 1 of 6		NP_476498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP26A1	ENST00000224356.5	c.97G>T	p.Val33Leu	missense_variant	Exon 1 of 7	1	NM_000783.4	ENSP00000224356.4
CYP26A1	ENST00000371531.5	c.-19+197G>T		intron_variant	Intron 1 of 6	2		ENSP00000360586.1
ENSG00000285846	ENST00000648258.1	n.892-1795G>T		intron_variant	Intron 1 of 3
CYP26A1	ENST00000622925.1	n.-47G>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	17
DANN	Benign	0.89
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.36	N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.039
Sift	Benign	0.50	T
Sift4G	Benign	0.68	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.37		Gain of catalytic residue at V33 (P = 0.0578);
MVP		0.77
MPC		1.0
ClinPred		0.32	T
GERP RS		1.8
Varity_R		0.078
gMVP		0.38

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

Other links and lift over

dbSNP: rs1293795438; hg19: chr10-94833788;