NM_177538.3:c.71C>G

Variant names:

• chr2-203239133-C-G
• rs2066147318
• NM_177538.3:c.71C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_177538.3(CYP20A1):​c.71C>G​(p.Pro24Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000685 in 1,460,376 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P24Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CYP20A1 NM_177538.3 missense, splice_region
• Scores: Splicing: ADA: 0.6525
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.33
• Publications: 0 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]

ENSG00000289294 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.76

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.71C>G	p.Pro24Arg	missense splice_region	Exon 1 of 13	NP_803882.1	Q6UW02-1
	CYP20A1	NM_001371695.1		c.71C>G	p.Pro24Arg	missense splice_region	Exon 1 of 13	NP_001358624.1	E9PHG5
	CYP20A1	NM_001371696.1		c.-19C>G		splice_region	Exon 1 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.71C>G	p.Pro24Arg	missense splice_region	Exon 1 of 13	ENSP00000348380.4	Q6UW02-1
	CYP20A1	ENST00000449301.5	TSL:1	n.71C>G		splice_region non_coding_transcript_exon	Exon 1 of 12	ENSP00000414831.1	F8WBE2
	CYP20A1	ENST00000875109.1		c.71C>G	p.Pro24Arg	missense splice_region	Exon 1 of 14	ENSP00000545168.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460376 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726602

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111354

Other (OTH) AF: 0.00 AC: 0 AN: 60338

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.84	T
M_CAP	Pathogenic	0.52	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Uncertain	-0.040	T
MutationAssessor	Benign	1.8	L
PhyloP100		6.3
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.012	D
Polyphen		0.99	D
Vest4		0.79
MutPred		0.50		Gain of methylation at P24 (P = 0.0082)
MVP		0.86
MPC		0.49
ClinPred		1.0	D
GERP RS		4.7
PromoterAI		-0.058	Neutral
Varity_R		0.59
gMVP		0.68
Mutation Taster		=8/92	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.65
dbscSNV1_RF	Benign	0.44
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: rs2066147318; hg19: chr2-204103856;