10-93074423-T-C

Variant names:

• chr10-93074423-T-C
• rs754298579
• NM_000783.4:c.305T>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_000783.4(CYP26A1):​c.305T>C​(p.Leu102Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CYP26A1 NM_000783.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.92

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.862

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP26A1	NM_000783.4	c.305T>C	p.Leu102Pro	missense_variant	Exon 2 of 7	ENST00000224356.5	NP_000774.2
CYP26A1	NM_057157.2	c.98T>C	p.Leu33Pro	missense_variant	Exon 2 of 7		NP_476498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP26A1	ENST00000224356.5	c.305T>C	p.Leu102Pro	missense_variant	Exon 2 of 7	1	NM_000783.4	ENSP00000224356.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459984 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726458

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.89
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	.;D
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.86	D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Uncertain	2.9	.;M
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Uncertain	0.62
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		0.99	.;D
Vest4		0.91
MutPred		0.57		.;Loss of stability (P = 0.023);
MVP		0.93
MPC		2.8
ClinPred		1.0	D
GERP RS		3.9
Varity_R		0.94
gMVP		0.92

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: rs754298579; hg19: chr10-94834180;