2-203289785-G-T

Variant names:

• chr2-203289785-G-T
• rs755461089
• NM_177538.3:c.992G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_177538.3(CYP20A1):​c.992G>T​(p.Cys331Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000141 in 1,420,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. C331Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CYP20A1 NM_177538.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.66
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3442898).

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.992G>T	p.Cys331Phe	missense	Exon 10 of 13	NP_803882.1	Q6UW02-1
	CYP20A1	NM_001371695.1		c.1016G>T	p.Cys339Phe	missense	Exon 10 of 13	NP_001358624.1	E9PHG5
	CYP20A1	NM_001371696.1		c.686G>T	p.Cys229Phe	missense	Exon 8 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.992G>T	p.Cys331Phe	missense	Exon 10 of 13	ENSP00000348380.4	Q6UW02-1
	CYP20A1	ENST00000449301.5	TSL:1	n.*286G>T		non_coding_transcript_exon	Exon 9 of 12	ENSP00000414831.1	F8WBE2
	CYP20A1	ENST00000449301.5	TSL:1	n.*286G>T		3_prime_UTR	Exon 9 of 12	ENSP00000414831.1	F8WBE2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1420758 Hom.: 0 Cov.: 28 AF XY: 0.00000142 AC XY: 1 AN XY: 706086

African (AFR) AF: 0.00 AC: 0 AN: 32128

American (AMR) AF: 0.00 AC: 0 AN: 39572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24934

East Asian (EAS) AF: 0.00 AC: 0 AN: 37894

South Asian (SAS) AF: 0.00 AC: 0 AN: 78468

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52428

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5644

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1091282

Other (OTH) AF: 0.0000342 AC: 2 AN: 58408

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.057	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.043
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.7
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.22
Sift	Benign	0.042	D
Sift4G	Benign	0.085	T
Polyphen		0.0030	B
Vest4		0.26
MutPred		0.62		Loss of catalytic residue at T341 (P = 0.0704)
MVP		0.83
MPC		0.17
ClinPred		0.82	D
GERP RS		3.7
Varity_R		0.53
gMVP		0.54
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs755461089; hg19: chr2-204154508;