Variant 6-46636408-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_016593.5(CYP39A1):c.713C>G(p.Ser238Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00402 in 1,605,750 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0032 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 14 hom. )

Consequence

CYP39A1
NM_016593.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.18

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056509376).

BP6

Variant 6-46636408-G-C is Benign according to our data. Variant chr6-46636408-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2656619.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP39A1	NM_016593.5 linkuse as main transcript	c.713C>G	p.Ser238Cys	missense_variant	5/12	ENST00000275016.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CYP39A1	ENST00000275016.3 linkuse as main transcript	c.713C>G	p.Ser238Cys	missense_variant	5/12	1	NM_016593.5	P1
CYP39A1	ENST00000619708.4 linkuse as main transcript	c.197C>G	p.Ser66Cys	missense_variant	4/11	1
CYP39A1	ENST00000480804.1 linkuse as main transcript	n.132C>G		non_coding_transcript_exon_variant	2/5	5

Frequencies

GnomAD3 genomes

AF:

0.00319

AC:

485

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00506

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00311

AC:

769

AN:

247544

Hom.:

AF XY:

0.00302

AC XY:

404

AN XY:

133570

show subpopulations

Gnomad AFR exome

AF:

0.000744

Gnomad AMR exome

AF:

0.00195

Gnomad ASJ exome

AF:

0.00370

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000343

Gnomad FIN exome

AF:

0.00185

Gnomad NFE exome

AF:

0.00526

Gnomad OTH exome

AF:

0.00364

GnomAD4 exome

AF:

0.00411

AC:

5970

AN:

1453486

Hom.:

Cov.:

AF XY:

0.00399

AC XY:

2881

AN XY:

722798

show subpopulations

Gnomad4 AFR exome

AF:

0.000842

Gnomad4 AMR exome

AF:

0.00197

Gnomad4 ASJ exome

AF:

0.00457

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000355

Gnomad4 FIN exome

AF:

0.00174

Gnomad4 NFE exome

AF:

0.00485

Gnomad4 OTH exome

AF:

0.00418

GnomAD4 genome

AF:

0.00319

AC:

485

AN:

152264

Hom.:

Cov.:

AF XY:

0.00290

AC XY:

216

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000578

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00170

Gnomad4 NFE

AF:

0.00506

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00434

Hom.:

Bravo

AF:

0.00352

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00606

AC:

ExAC

AF:

0.00308

AC:

374

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

CYP39A1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.032

.;T

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.0057

T;T

MetaSVM

Uncertain

-0.18

MutationAssessor

Uncertain

2.3

.;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.5

.;N

REVEL

Uncertain

0.36

Sift

Uncertain

0.014

.;D

Sift4G

Uncertain

0.054

T;T

Polyphen

0.99

.;D

Vest4

0.17

MVP

0.90

MPC

0.25

ClinPred

0.015

GERP RS

5.2

Varity_R

0.15

gMVP

0.30

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over