chr2-203252041-A-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001371702.1(CYP20A1):​c.-242A>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,460,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: CYP20A1 NM_001371702.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08145812).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371702.1. 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>C	p.Met122Leu	missense	Exon 4 of 13	NP_803882.1	Q6UW02-1
	CYP20A1	NM_001371702.1		c.-242A>C		5_prime_UTR_premature_start_codon_gain	Exon 3 of 11	NP_001358631.1
	CYP20A1	NM_001371703.1		c.-242A>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 10	NP_001358632.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP20A1	ENST00000356079.9	TSL:1 MANE Select	c.364A>C	p.Met122Leu	missense	Exon 4 of 13	ENSP00000348380.4	Q6UW02-1
	CYP20A1	ENST00000449301.5	TSL:1	n.364A>C		non_coding_transcript_exon	Exon 4 of 12	ENSP00000414831.1	F8WBE2
	CYP20A1	ENST00000875109.1		c.364A>C	p.Met122Leu	missense	Exon 4 of 14	ENSP00000545168.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 250352 AF XY: 0.0000148

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000890 AC: 13 AN: 1460146 Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8 AN XY: 726430

African (AFR) AF: 0.00 AC: 0 AN: 33426

American (AMR) AF: 0.00 AC: 0 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39564

South Asian (SAS) AF: 0.00 AC: 0 AN: 86038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111032

Other (OTH) AF: 0.0000166 AC: 1 AN: 60304

GnomAD4 genome Cov.: 27

Alfa AF: 0.00000453 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	8.0
DANN	Benign	0.44
DEOGEN2	Benign	0.031	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.20	N
PhyloP100		0.44
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.17
Sift	Benign	0.46	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.55		Gain of catalytic residue at M122 (P = 0.0516)
MVP		0.62
MPC		0.10
ClinPred		0.013	T
GERP RS		-3.2
Varity_R		0.036
gMVP		0.30
Mutation Taster		=98/2	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;