rs761575210

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_183075.3(CYP2U1):​c.452C>A​(p.Pro151Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,446,892 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: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CYP2U1
NM_183075.3 missense

Scores

6
10
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.66
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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, 0.888

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CYP2U1NM_183075.3 linkuse as main transcriptc.452C>A p.Pro151Gln missense_variant 1/5 ENST00000332884.11 NP_898898.1 Q7Z449-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CYP2U1ENST00000332884.11 linkuse as main transcriptc.452C>A p.Pro151Gln missense_variant 1/51 NM_183075.3 ENSP00000333212.6 Q7Z449-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000922
AC:
2
AN:
216904
Hom.:
0
AF XY:
0.00000842
AC XY:
1
AN XY:
118804
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000620
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000104
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1446892
Hom.:
0
Cov.:
31
AF XY:
0.00000139
AC XY:
1
AN XY:
718384
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000258
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.04e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.0000250
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingMayo Clinic Laboratories, Mayo ClinicFeb 04, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.89
BayesDel_addAF
Benign
-0.027
T
BayesDel_noAF
Benign
-0.090
CADD
Pathogenic
29
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.43
T
Eigen
Pathogenic
0.75
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.91
D
M_CAP
Pathogenic
0.63
D
MetaRNN
Pathogenic
0.89
D
MetaSVM
Uncertain
0.60
D
MutationAssessor
Pathogenic
3.5
H
PrimateAI
Uncertain
0.63
T
PROVEAN
Pathogenic
-6.6
D
REVEL
Uncertain
0.61
Sift
Uncertain
0.026
D
Sift4G
Uncertain
0.0090
D
Polyphen
1.0
D
Vest4
0.69
MutPred
0.55
Loss of stability (P = 0.0756);
MVP
0.83
MPC
0.55
ClinPred
0.98
D
GERP RS
3.6
Varity_R
0.58
gMVP
0.79

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs761575210; hg19: chr4-108853251; API