2-203280101-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000356079.9(CYP20A1):ā€‹c.838A>Gā€‹(p.Ile280Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000517 in 1,606,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 33)
Exomes š‘“: 0.000054 ( 0 hom. )

Consequence

CYP20A1
ENST00000356079.9 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.74
Variant links:
Genes affected
CYP20A1 (HGNC:20576): (cytochrome P450 family 20 subfamily A member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein lacks one amino acid of the conserved heme binding site. It also lacks the conserved I-helix motif AGX(D,E)T, suggesting that its substrate may carry its own oxygen. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.19750354).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CYP20A1NM_177538.3 linkuse as main transcriptc.838A>G p.Ile280Val missense_variant 8/13 ENST00000356079.9 NP_803882.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CYP20A1ENST00000356079.9 linkuse as main transcriptc.838A>G p.Ile280Val missense_variant 8/131 NM_177538.3 ENSP00000348380 P1Q6UW02-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152176
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000122
AC:
3
AN:
246744
Hom.:
0
AF XY:
0.00000749
AC XY:
1
AN XY:
133528
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000266
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000536
AC:
78
AN:
1453954
Hom.:
0
Cov.:
28
AF XY:
0.0000498
AC XY:
36
AN XY:
723310
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000677
Gnomad4 OTH exome
AF:
0.0000499
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152294
Hom.:
0
Cov.:
33
AF XY:
0.0000537
AC XY:
4
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 02, 2024The c.838A>G (p.I280V) alteration is located in exon 8 (coding exon 8) of the CYP20A1 gene. This alteration results from a A to G substitution at nucleotide position 838, causing the isoleucine (I) at amino acid position 280 to be replaced by a valine (V). 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
0.11
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
16
DANN
Benign
0.97
DEOGEN2
Benign
0.022
T;T;T;T
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.20
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.81
T;T;T;T
M_CAP
Benign
0.0073
T
MetaRNN
Benign
0.20
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.2
L;.;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.48
T
PROVEAN
Benign
0.32
N;N;.;N
REVEL
Benign
0.055
Sift
Benign
0.20
T;T;.;T
Sift4G
Benign
0.10
T;T;T;D
Polyphen
0.0080
B;B;.;.
Vest4
0.27
MutPred
0.63
.;Gain of catalytic residue at I288 (P = 0.0179);.;.;
MVP
0.54
MPC
0.093
ClinPred
0.15
T
GERP RS
2.1
Varity_R
0.17
gMVP
0.12

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: rs371111502; hg19: chr2-204144824; API