Variant 6-46625485-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_016593.5(CYP39A1):c.864C>T(p.Tyr288=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000574 in 1,609,276 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00050 ( 1 hom. )

Consequence

CYP39A1
NM_016593.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.55

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 6-46625485-G-A is Benign according to our data. Variant chr6-46625485-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3079613.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.55 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP39A1	NM_016593.5 linkuse as main transcript	c.864C>T	p.Tyr288=	synonymous_variant	7/12	ENST00000275016.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CYP39A1	ENST00000275016.3 linkuse as main transcript	c.864C>T	p.Tyr288=	synonymous_variant	7/12	1	NM_016593.5	P1
CYP39A1	ENST00000619708.4 linkuse as main transcript	c.348C>T	p.Tyr116=	synonymous_variant	6/11	1
CYP39A1	ENST00000480804.1 linkuse as main transcript	n.175C>T		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes

AF:

0.00122

AC:

185

AN:

152022

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.000842

AC:

210

AN:

249332

Hom.:

AF XY:

0.000928

AC XY:

125

AN XY:

134740

show subpopulations

Gnomad AFR exome

AF:

0.00167

Gnomad AMR exome

AF:

0.00115

Gnomad ASJ exome

AF:

0.00668

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000299

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000504

Gnomad OTH exome

AF:

0.00181

GnomAD4 exome

AF:

0.000501

AC:

730

AN:

1457136

Hom.:

Cov.:

AF XY:

0.000523

AC XY:

379

AN XY:

724846

show subpopulations

Gnomad4 AFR exome

AF:

0.00216

Gnomad4 AMR exome

AF:

0.00117

Gnomad4 ASJ exome

AF:

0.00608

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000364

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000298

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.00127

AC:

193

AN:

152140

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

100

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00238

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.000798

Hom.:

Bravo

AF:

0.00146

Asia WGS

AF:

0.00202

AC:

AN:

3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.2

DANN

Benign

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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