NM_177538.3:c.364A>G

Variant names:

• chr2-203252041-A-G
• rs200681711
• NM_177538.3:c.364A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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. 17/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.444
• Publications: 5 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0115174055).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177538.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP20A1	NM_177538.3	MANE Select	c.364A>G	p.Met122Val	missense	Exon 4 of 13	NP_803882.1	Q6UW02-1
	CYP20A1	NM_001371695.1		c.364A>G	p.Met122Val	missense	Exon 4 of 13	NP_001358624.1	E9PHG5
	CYP20A1	NM_001371696.1		c.58A>G	p.Met20Val	missense	Exon 2 of 11	NP_001358625.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP20A1	ENST00000356079.9	TSL:1 MANE Select	c.364A>G	p.Met122Val	missense	Exon 4 of 13	ENSP00000348380.4	Q6UW02-1
	CYP20A1	ENST00000449301.5	TSL:1	n.364A>G		non_coding_transcript_exon	Exon 4 of 12	ENSP00000414831.1	F8WBE2
	CYP20A1	ENST00000875109.1		c.364A>G	p.Met122Val	missense	Exon 4 of 14	ENSP00000545168.1

Frequencies

GnomAD3 genomes AF: 0.000409 AC: 62 AN: 151506 Hom.: 0 Cov.: 27

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

GnomAD2 exomes AF: 0.000447 AC: 112 AN: 250352 AF XY: 0.000443

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 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.: 2 Cov.: 32 AF XY: 0.000264 AC XY: 192 AN XY: 726430

African (AFR) AF: 0.0000898 AC: 3 AN: 33426

American (AMR) AF: 0.00150 AC: 67 AN: 44580

Ashkenazi Jewish (ASJ) AF: 0.00196 AC: 51 AN: 26078

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39564

South Asian (SAS) AF: 0.000349 AC: 30 AN: 86038

European-Finnish (FIN) AF: 0.000337 AC: 18 AN: 53362

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5760

European-Non Finnish (NFE) AF: 0.000136 AC: 151 AN: 1111032

Other (OTH) AF: 0.000448 AC: 27 AN: 60304

GnomAD4 genome AF: 0.000409 AC: 62 AN: 151624 Hom.: 0 Cov.: 27 AF XY: 0.000419 AC XY: 31 AN XY: 74064

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.00291 AC: 44 AN: 15130

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3468

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10450

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67908

Other (OTH) AF: 0.00144 AC: 3 AN: 2088

Alfa AF: 0.000471 Hom.: 0

Bravo AF: 0.000567

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.000404 AC: 49

EpiCase AF: 0.000164

EpiControl AF: 0.000536

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	8.3
DANN	Benign	0.50
DEOGEN2	Benign	0.035	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PhyloP100		0.44
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.16
Sift	Benign	0.58	T
Sift4G	Benign	0.89	T
Polyphen		0.0	B
Vest4		0.076
MVP		0.64
MPC		0.11
ClinPred		0.0037	T
GERP RS		-3.2
Varity_R		0.031
gMVP		0.32
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs200681711; hg19: chr2-204116764;