10-93074020-A-G

Position:

• chr10-93074020-A-G

Variant summary

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

The ENST00000224356.5(CYP26A1):​c.86A>G​(p.Asp29Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CYP26A1 ENST00000224356.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.78

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]

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=0.2135).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP26A1	NM_000783.4	c.86A>G	p.Asp29Gly	missense_variant	1/7	ENST00000224356.5	NP_000774.2
CYP26A1	NM_057157.2	c.-19+186A>G		intron_variant			NP_476498.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP26A1	ENST00000224356.5	c.86A>G	p.Asp29Gly	missense_variant	1/7	1	NM_000783.4	ENSP00000224356	P1
CYP26A1	ENST00000371531.5	c.-19+186A>G		intron_variant		2		ENSP00000360586

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 10, 2022

The c.86A>G (p.D29G) alteration is located in exon 1 (coding exon 1) of the CYP26A1 gene. This alteration results from a A to G substitution at nucleotide position 86, causing the aspartic acid (D) at amino acid position 29 to be replaced by a glycine (G). 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	0.13
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.083	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.028
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.10
Sift	Benign	0.35	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.25
MutPred		0.48		Gain of ubiquitination at K26 (P = 0.0725);
MVP		0.87
MPC		1.4
ClinPred		0.76	D
GERP RS		4.9
Varity_R		0.29
gMVP		0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-94833777;