Variant rs12192544 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016593.5(CYP39A1):c.68G>C(p.Arg23Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,612,888 control chromosomes in the GnomAD database, including 38,328 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.17 ( 2676 hom., cov: 32)

Exomes 𝑓: 0.22 ( 35652 hom. )

Consequence

CYP39A1
NM_016593.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.154

Variant links:

Genes affected

CYP39A1 (HGNC:17449): (cytochrome P450 family 39 subfamily A member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This endoplasmic reticulum protein is involved in the conversion of cholesterol to bile acids. Its substrates include the oxysterols 25-hydroxycholesterol, 27-hydroxycholesterol and 24-hydroxycholesterol. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

CYP39A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033367872).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP39A1	NM_016593.5 linkuse as main transcript	c.68G>C	p.Arg23Pro	missense_variant	1/12	ENST00000275016.3	NP_057677.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP39A1	ENST00000275016.3 linkuse as main transcript	c.68G>C	p.Arg23Pro	missense_variant	1/12	1	NM_016593.5	ENSP00000275016	P1
CYP39A1	ENST00000619708.4 linkuse as main transcript	c.-274G>C		5_prime_UTR_variant	1/11	1		ENSP00000477769

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25446

AN:

152022

Hom.:

2674

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0498

Gnomad AMI

AF:

0.223

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.285

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.224

Gnomad OTH

AF:

0.180

GnomAD3 exomes

AF:

0.201

AC:

50347

AN:

250374

Hom.:

5726

AF XY:

0.211

AC XY:

28545

AN XY:

135336

show subpopulations

Gnomad AFR exome

AF:

0.0451

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.304

Gnomad EAS exome

AF:

0.133

Gnomad SAS exome

AF:

0.284

Gnomad FIN exome

AF:

0.223

Gnomad NFE exome

AF:

0.224

Gnomad OTH exome

AF:

0.203

GnomAD4 exome

AF:

0.216

AC:

316200

AN:

1460750

Hom.:

35652

Cov.:

AF XY:

0.220

AC XY:

159628

AN XY:

726620

show subpopulations

Gnomad4 AFR exome

AF:

0.0422

Gnomad4 AMR exome

AF:

0.122

Gnomad4 ASJ exome

AF:

0.299

Gnomad4 EAS exome

AF:

0.120

Gnomad4 SAS exome

AF:

0.286

Gnomad4 FIN exome

AF:

0.220

Gnomad4 NFE exome

AF:

0.222

Gnomad4 OTH exome

AF:

0.209

GnomAD4 genome

AF:

0.167

AC:

25447

AN:

152138

Hom.:

2676

Cov.:

AF XY:

0.168

AC XY:

12473

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0498

Gnomad4 AMR

AF:

0.139

Gnomad4 ASJ

AF:

0.285

Gnomad4 EAS

AF:

0.132

Gnomad4 SAS

AF:

0.283

Gnomad4 FIN

AF:

0.224

Gnomad4 NFE

AF:

0.224

Gnomad4 OTH

AF:

0.182

Alfa

AF:

0.218

Hom.:

2989

Bravo

AF:

0.151

TwinsUK

AF:

0.221

AC:

818

ALSPAC

AF:

0.229

AC:

881

ESP6500AA

AF:

0.0520

AC:

229

ESP6500EA

AF:

0.230

AC:

1980

ExAC

AF:

0.202

AC:

24539

Asia WGS

AF:

0.172

AC:

601

AN:

3478

EpiCase

AF:

0.222

EpiControl

AF:

0.223

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0033

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.5

REVEL

Benign

0.18

Sift

Benign

0.12

Sift4G

Benign

0.21

Polyphen

0.96

Vest4

0.029

MPC

0.050

ClinPred

0.015

GERP RS

3.4

Varity_R

0.22

gMVP

0.55

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over