rs772136947
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_183075.3(CYP2U1):c.1630A>T(p.Arg544Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.0000493 in 1,602,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000050 ( 0 hom. )
Consequence
CYP2U1
NM_183075.3 stop_gained
NM_183075.3 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 3.62
Genes affected
CYP2U1 (HGNC:20582): (cytochrome P450 family 2 subfamily U 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 a hydroxylase that metabolizes arachidonic acid, docosahexaenoic acid, and other long chain fatty acids. [provided by RefSeq, Jul 2008]
CYP2U1-AS1 (HGNC:54817): (CYP2U1 and SGMS2 antisense RNA 1)
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.00306 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP2U1 | NM_183075.3 | c.1630A>T | p.Arg544Ter | stop_gained | 5/5 | ENST00000332884.11 | |
LOC107986298 | XR_001741784.2 | n.204+28302T>A | intron_variant, non_coding_transcript_variant | ||||
CYP2U1 | XM_005262717.2 | c.1684A>T | p.Arg562Ter | stop_gained | 5/5 | ||
CYP2U1 | XM_005262720.2 | c.994A>T | p.Arg332Ter | stop_gained | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP2U1 | ENST00000332884.11 | c.1630A>T | p.Arg544Ter | stop_gained | 5/5 | 1 | NM_183075.3 | P1 | |
CYP2U1-AS1 | ENST00000656249.1 | n.80+28302T>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152154Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000336 AC: 8AN: 237970Hom.: 0 AF XY: 0.0000311 AC XY: 4AN XY: 128754
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GnomAD4 exome AF: 0.0000496 AC: 72AN: 1450342Hom.: 0 Cov.: 30 AF XY: 0.0000444 AC XY: 32AN XY: 721444
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GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74334
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2019 | - - |
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2022 | This sequence change creates a premature translational stop signal (p.Arg544*) in the CYP2U1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1 amino acid(s) of the CYP2U1 protein. This variant is present in population databases (rs772136947, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CYP2U1-related conditions. ClinVar contains an entry for this variant (Variation ID: 572643). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D;N
Vest4
GERP RS
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