10-93061447-A-T
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_183374.3(CYP26C1):c.184A>T(p.Thr62Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000425 in 1,552,360 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0022 ( 3 hom., cov: 33)
Exomes 𝑓: 0.00023 ( 1 hom. )
Consequence
CYP26C1
NM_183374.3 missense
NM_183374.3 missense
Scores
12
6
Clinical Significance
Conservation
PhyloP100: 5.92
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.016737044).
BP6
Variant 10-93061447-A-T is Benign according to our data. Variant chr10-93061447-A-T is described in ClinVar as [Benign]. Clinvar id is 717978.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CYP26C1 | NM_183374.3 | c.184A>T | p.Thr62Ser | missense_variant | 1/6 | ENST00000651965.1 | NP_899230.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CYP26C1 | ENST00000651965.1 | c.184A>T | p.Thr62Ser | missense_variant | 1/6 | NM_183374.3 | ENSP00000498424 | P1 | ||
CYP26C1 | ENST00000624358.3 | c.184A>T | p.Thr62Ser | missense_variant, NMD_transcript_variant | 1/6 | 2 | ENSP00000485098 |
Frequencies
GnomAD3 genomes AF: 0.00224 AC: 341AN: 152084Hom.: 3 Cov.: 33
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GnomAD3 exomes AF: 0.000624 AC: 94AN: 150656Hom.: 1 AF XY: 0.000375 AC XY: 30AN XY: 79994
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GnomAD4 exome AF: 0.000227 AC: 318AN: 1400158Hom.: 1 Cov.: 31 AF XY: 0.000197 AC XY: 136AN XY: 690846
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GnomAD4 genome AF: 0.00225 AC: 342AN: 152202Hom.: 3 Cov.: 33 AF XY: 0.00218 AC XY: 162AN XY: 74418
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 13, 2018 | - - |
CYP26C1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 22, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
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ClinPred
T
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at