Genetic Variant CYP20A1:p.Met122Val (chr2-203252041-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_177538.3(CYP20A1):c.364A>G(p.Met122Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000256 in 1,611,768 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 27)

Exomes 𝑓: 0.00024 ( 2 hom. )

Consequence

CYP20A1
NM_177538.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.444

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0115174055).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP20A1	NM_177538.3 link	c.364A>G	p.Met122Val	missense_variant	Exon 4 of 13	ENST00000356079.9	NP_803882.1	Q6UW02-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP20A1	ENST00000356079.9 link	c.364A>G	p.Met122Val	missense_variant	Exon 4 of 13	1	NM_177538.3	ENSP00000348380.4		Q6UW02-1

Frequencies

GnomAD3 genomes

AF:

0.000409

AC:

AN:

151506

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00291

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00145

GnomAD3 exomes

AF:

0.000447

AC:

112

AN:

250352

Hom.:

AF XY:

0.000443

AC XY:

AN XY:

135370

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00114

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000361

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.000987

GnomAD4 exome

AF:

0.000240

AC:

351

AN:

1460144

Hom.:

Cov.:

AF XY:

0.000264

AC XY:

192

AN XY:

726430

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.00150

Gnomad4 ASJ exome

AF:

0.00196

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000349

Gnomad4 FIN exome

AF:

0.000337

Gnomad4 NFE exome

AF:

0.000136

Gnomad4 OTH exome

AF:

0.000448

GnomAD4 genome

AF:

0.000409

AC:

AN:

151624

Hom.:

Cov.:

AF XY:

0.000419

AC XY:

AN XY:

74064

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00291

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00144

Alfa

AF:

0.000303

Hom.:

Bravo

AF:

0.000567

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000404

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000536

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.364A>G (p.M122V) alteration is located in exon 4 (coding exon 4) of the CYP20A1 gene. This alteration results from a A to G substitution at nucleotide position 364, causing the methionine (M) at amino acid position 122 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

0.062

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.43

CADD

Benign

8.3

DANN

Benign

0.50

DEOGEN2

Benign

0.035

T;T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.012

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;.;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.75

N;N;N

REVEL

Benign

0.16

Sift

Benign

0.58

T;T;T

Sift4G

Benign

0.89

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.076

MVP

0.64

MPC

0.11

ClinPred

0.0037

GERP RS

-3.2

Varity_R

0.031

gMVP

0.32

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