Variant 2-203289852-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000356079.9(CYP20A1):c.1059T>G(p.Ile353Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000991 in 1,586,504 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0054 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00053 ( 6 hom. )

Consequence

CYP20A1
ENST00000356079.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0770

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]

CYP20A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006091565).

BP6

Variant 2-203289852-T-G is Benign according to our data. Variant chr2-203289852-T-G is described in ClinVar as [Benign]. Clinvar id is 783349.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00537 (818/152268) while in subpopulation AFR AF= 0.0188 (779/41540). AF 95% confidence interval is 0.0177. There are 7 homozygotes in gnomad4. There are 392 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP20A1	NM_177538.3 linkuse as main transcript	c.1059T>G	p.Ile353Met	missense_variant	10/13	ENST00000356079.9	NP_803882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP20A1	ENST00000356079.9 linkuse as main transcript	c.1059T>G	p.Ile353Met	missense_variant	10/13	1	NM_177538.3	ENSP00000348380	P1	Q6UW02-1

Frequencies

GnomAD3 genomes

AF:

0.00533

AC:

811

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

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:

0.0000441

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00129

AC:

310

AN:

240376

Hom.:

AF XY:

0.000914

AC XY:

119

AN XY:

130130

show subpopulations

Gnomad AFR exome

AF:

0.0175

Gnomad AMR exome

AF:

0.000849

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:

0.0000364

Gnomad OTH exome

AF:

0.000700

GnomAD4 exome

AF:

0.000526

AC:

754

AN:

1434236

Hom.:

Cov.:

AF XY:

0.000448

AC XY:

320

AN XY:

713972

show subpopulations

Gnomad4 AFR exome

AF:

0.0181

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000363

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000338

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.00537

AC:

818

AN:

152268

Hom.:

Cov.:

AF XY:

0.00527

AC XY:

392

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0188

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00111

Hom.:

Bravo

AF:

0.00636

ESP6500AA

AF:

0.0188

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00181

AC:

220

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	Apr 19, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.11

T;T;T

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.80

T;T;T

MetaRNN

Benign

0.0061

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.2

L;.;.

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.6

N;N;.

REVEL

Benign

0.15

Sift

Uncertain

0.0020

D;D;.

Sift4G

Uncertain

0.0070

D;D;T

Polyphen

0.051

B;B;.

Vest4

0.34

MVP

0.57

MPC

0.14

ClinPred

0.037

GERP RS

-0.66

Varity_R

0.32

gMVP

0.46

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over