Variant 6-46596080-A-T 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.972T>A(p.Asn324Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 1,607,776 control chromosomes in the GnomAD database, including 82,804 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.39 ( 13664 hom., cov: 31)

Exomes 𝑓: 0.29 ( 69140 hom. )

Consequence

CYP39A1
NM_016593.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0120

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:

RCAN2-DT (HGNC:55661): (RCAN2 divergent transcript)

RCAN2-DT 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=4.743546E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP39A1	NM_016593.5 link	c.972T>A	p.Asn324Lys	missense_variant	Exon 8 of 12	ENST00000275016.3	NP_057677.2	Q9NYL5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CYP39A1	ENST00000275016.3 link	c.972T>A	p.Asn324Lys	missense_variant	Exon 8 of 12	1	NM_016593.5	ENSP00000275016.2	Q9NYL5
CYP39A1	ENST00000619708.4 link	c.456T>A	p.Asn152Lys	missense_variant	Exon 7 of 11	1		ENSP00000477769.1	A0A087WTD2
CYP39A1	ENST00000480804.1 link	n.283T>A		non_coding_transcript_exon_variant	Exon 4 of 5	5
RCAN2-DT	ENST00000657801.1 link	n.287-9851A>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.386

AC:

58578

AN:

151570

Hom.:

13616

Cov.:

show subpopulations

Gnomad AFR

AF:

0.639

Gnomad AMI

AF:

0.142

Gnomad AMR

AF:

0.397

Gnomad ASJ

AF:

0.356

Gnomad EAS

AF:

0.348

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.220

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.250

Gnomad OTH

AF:

0.381

GnomAD3 exomes

AF:

0.347

AC:

86656

AN:

249442

Hom.:

17659

AF XY:

0.349

AC XY:

47066

AN XY:

134848

show subpopulations

Gnomad AFR exome

AF:

0.647

Gnomad AMR exome

AF:

0.398

Gnomad ASJ exome

AF:

0.367

Gnomad EAS exome

AF:

0.317

Gnomad SAS exome

AF:

0.579

Gnomad FIN exome

AF:

0.222

Gnomad NFE exome

AF:

0.255

Gnomad OTH exome

AF:

0.339

GnomAD4 exome

AF:

0.288

AC:

419965

AN:

1456088

Hom.:

69140

Cov.:

AF XY:

0.296

AC XY:

214116

AN XY:

724364

show subpopulations

Gnomad4 AFR exome

AF:

0.665

Gnomad4 AMR exome

AF:

0.398

Gnomad4 ASJ exome

AF:

0.362

Gnomad4 EAS exome

AF:

0.400

Gnomad4 SAS exome

AF:

0.571

Gnomad4 FIN exome

AF:

0.228

Gnomad4 NFE exome

AF:

0.245

Gnomad4 OTH exome

AF:

0.326

GnomAD4 genome

AF:

0.387

AC:

58680

AN:

151688

Hom.:

13664

Cov.:

AF XY:

0.388

AC XY:

28798

AN XY:

74148

show subpopulations

Gnomad4 AFR

AF:

0.640

Gnomad4 AMR

AF:

0.398

Gnomad4 ASJ

AF:

0.356

Gnomad4 EAS

AF:

0.346

Gnomad4 SAS

AF:

0.587

Gnomad4 FIN

AF:

0.220

Gnomad4 NFE

AF:

0.250

Gnomad4 OTH

AF:

0.384

Alfa

AF:

0.280

Hom.:

4981

Bravo

AF:

0.402

TwinsUK

AF:

0.242

AC:

897

ALSPAC

AF:

0.241

AC:

930

ESP6500AA

AF:

0.628

AC:

2767

ESP6500EA

AF:

0.267

AC:

2293

ExAC

AF:

0.356

AC:

43177

Asia WGS

AF:

0.512

AC:

1777

AN:

3474

EpiCase

AF:

0.269

EpiControl

AF:

0.270

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

CADD

Benign

6.5

DANN

Benign

0.72

DEOGEN2

Benign

0.0060

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.30

T;T

MetaRNN

Benign

0.000047

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.0

.;N

PrimateAI

Benign

0.36

PROVEAN

Benign

1.6

.;N

REVEL

Benign

0.22

Sift

Benign

1.0

.;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.079

MutPred

0.17

.;Gain of ubiquitination at N324 (P = 0.0337);

MPC

0.042

ClinPred

0.00054

GERP RS

-0.55

Varity_R

0.064

gMVP

0.25

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