Variant 2-203285687-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_177538.3(CYP20A1):c.926T>C(p.Val309Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,452,254 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

CYP20A1
NM_177538.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.11

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:

CYP20A1 (HGNC:):

CYP20A1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP20A1	NM_177538.3 linkuse as main transcript	c.926T>C	p.Val309Ala	missense_variant	9/13	ENST00000356079.9	NP_803882.1	Q6UW02-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP20A1	ENST00000356079.9 linkuse as main transcript	c.926T>C	p.Val309Ala	missense_variant	9/13	1	NM_177538.3	ENSP00000348380.4		Q6UW02-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000413

AC:

AN:

242260

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131256

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:

0.0000356

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1452254

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722442

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:

0.0000477

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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 submitter

clinical testing

Ambry Genetics

Jan 04, 2022

The c.926T>C (p.V309A) alteration is located in exon 9 (coding exon 9) of the CYP20A1 gene. This alteration results from a T to C substitution at nucleotide position 926, causing the valine (V) at amino acid position 309 to be replaced by an alanine (A). 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

0.18

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.075

T;T;T;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.74

T;T;T;T

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.70

D;D;D;D

MetaSVM

Uncertain

0.15

MutationAssessor

Uncertain

2.1

M;.;.;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-2.4

N;N;.;N

REVEL

Uncertain

0.34

Sift

Uncertain

0.023

D;D;.;D

Sift4G

Uncertain

0.011

D;D;D;D

Polyphen

0.99

D;P;.;.

Vest4

0.75

MutPred

0.67

.;Loss of stability (P = 0.1093);.;.;

MVP

0.84

MPC

0.55

ClinPred

0.84

GERP RS

5.6

Varity_R

0.64

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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