rs1047303

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000862.3(HSD3B1):c.1100C>A(p.Thr367Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 1,613,074 control chromosomes in the GnomAD database, including 412,097 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign,drug response (★★).

Frequency

Genomes: 𝑓 0.76 ( 44941 hom., cov: 29)

Exomes 𝑓: 0.71 ( 367156 hom. )

Consequence

HSD3B1
NM_000862.3 missense

Scores

Clinical Significance

Benign; drug response criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -0.311

Publications

94 publications found

Variant links:

Genes affected

HSD3B1 (HGNC:5217): (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1) The protein encoded by this gene is an enzyme that catalyzes the oxidative conversion of delta-5-3-beta-hydroxysteroid precursors into delta-4-ketosteroids, which leads to the production of all classes of steroid hormones. The encoded protein also catalyzes the interconversion of 3-beta-hydroxy- and 3-keto-5-alpha-androstane steroids. [provided by RefSeq, Jun 2016]

HSD3B1 links:

ENSG00000293080 (HGNC:):

ENSG00000293080 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.1095348E-6).

BP6

Variant 1-119514623-C-A is Benign according to our data. Variant chr1-119514623-C-A is described in ClinVar as Benign|drug_response. ClinVar VariationId is 1274004.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD3B1	NM_000862.3 link	c.1100C>A	p.Thr367Asn	missense_variant	Exon 4 of 4	ENST00000369413.8	NP_000853.1	P14060
HSD3B1	NM_001328615.1 link	c.1100C>A	p.Thr367Asn	missense_variant	Exon 4 of 4		NP_001315544.1	P14060

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD3B1	ENST00000369413.8 link	c.1100C>A	p.Thr367Asn	missense_variant	Exon 4 of 4	1	NM_000862.3	ENSP00000358421.3		P14060

Frequencies

GnomAD3 genomes

AF:

0.764

AC:

115773

AN:

151570

Hom.:

44897

Cov.:

show subpopulations

Gnomad AFR

AF:

0.884

Gnomad AMI

AF:

0.811

Gnomad AMR

AF:

0.789

Gnomad ASJ

AF:

0.670

Gnomad EAS

AF:

0.924

Gnomad SAS

AF:

0.826

Gnomad FIN

AF:

0.746

Gnomad MID

AF:

0.672

Gnomad NFE

AF:

0.677

Gnomad OTH

AF:

0.727

GnomAD2 exomes

AF:

0.755

AC:

188429

AN:

249654

AF XY:

0.748

show subpopulations

Gnomad AFR exome

AF:

0.892

Gnomad AMR exome

AF:

0.850

Gnomad ASJ exome

AF:

0.666

Gnomad EAS exome

AF:

0.937

Gnomad FIN exome

AF:

0.741

Gnomad NFE exome

AF:

0.674

Gnomad OTH exome

AF:

0.718

GnomAD4 exome

AF:

0.705

AC:

1030890

AN:

1461386

Hom.:

367156

Cov.:

AF XY:

0.707

AC XY:

513679

AN XY:

726994

show subpopulations

African (AFR)

AF:

0.895

AC:

29947

AN:

33472

American (AMR)

AF:

0.840

AC:

37513

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.670

AC:

17497

AN:

26128

East Asian (EAS)

AF:

0.939

AC:

37206

AN:

39638

South Asian (SAS)

AF:

0.808

AC:

69644

AN:

86242

European-Finnish (FIN)

AF:

0.742

AC:

39651

AN:

53410

Middle Eastern (MID)

AF:

0.646

AC:

3721

AN:

5756

European-Non Finnish (NFE)

AF:

0.677

AC:

752348

AN:

1111690

Other (OTH)

AF:

0.718

AC:

43363

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

16739

33478

50216

66955

83694

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19528

39056

58584

78112

97640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.764

AC:

115875

AN:

151688

Hom.:

44941

Cov.:

AF XY:

0.771

AC XY:

57102

AN XY:

74092

show subpopulations

African (AFR)

AF:

0.884

AC:

36589

AN:

41384

American (AMR)

AF:

0.789

AC:

12014

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.670

AC:

2325

AN:

3468

East Asian (EAS)

AF:

0.924

AC:

4748

AN:

5140

South Asian (SAS)

AF:

0.825

AC:

3959

AN:

4798

European-Finnish (FIN)

AF:

0.746

AC:

7806

AN:

10470

Middle Eastern (MID)

AF:

0.675

AC:

197

AN:

292

European-Non Finnish (NFE)

AF:

0.677

AC:

45963

AN:

67898

Other (OTH)

AF:

0.731

AC:

1534

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1302

2603

3905

5206

6508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

848

1696

2544

3392

4240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.711

Hom.:

17051

Bravo

AF:

0.771

TwinsUK

AF:

0.675

AC:

2504

ALSPAC

AF:

0.671

AC:

2585

ESP6500AA

AF:

0.881

AC:

3879

ESP6500EA

AF:

0.682

AC:

5860

ExAC

AF:

0.755

AC:

91615

Asia WGS

AF:

0.866

AC:

3011

AN:

3478

EpiCase

AF:

0.657

EpiControl

AF:

0.659

ClinVar

Significance: Benign; drug response

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 14, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 31932420) -

Androgen deprivation therapy response

Other:1

Mar 01, 2024

Desai Sethi Urology Institute, University Of Miami

Significance:drug response

Review Status:criteria provided, single submitter

Collection Method:clinical testing;research

Slower development of castration-resistant prostate cancer has now been shown in at least 10 cohorts (Hearn, et al. Lancet Oncol. 2016 (PMID:27575027); Hearn, et al. JAMA Oncol. 2018 (PMID:29049492); Agarwal, et al. JAMA Oncol. 2017 (PMID:28208175)) and has shown to result in higher prostate cancer specific mortality rates in a cohort of over 5,000 patients (McKay, et al. JAMA Netw Open. 2024 (PMID:38506808)). More Responsive

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.078

(source)

DANN

Benign

0.26

DEOGEN2

Benign

0.14

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.24

.;T

MetaRNN

Benign

0.0000011

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;M

PhyloP100

-0.31

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.13

Sift

Benign

0.30

T;T

Sift4G

Benign

0.30

T;T

Polyphen

0.021

B;B

Vest4

0.093

MPC

0.029

ClinPred

0.0099

GERP RS

-0.043

Varity_R

0.046

gMVP

0.42

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over