1-119514623-C-A

Position:

chr1-119514623-C-A

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign,drug response (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
HSD3B1	NM_000862.3 linkuse as main transcript	c.1100C>A	p.Thr367Asn	missense_variant	4/4	ENST00000369413.8	NP_000853.1
HSD3B1	NM_001328615.1 linkuse as main transcript	c.1100C>A	p.Thr367Asn	missense_variant	4/4		NP_001315544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD3B1	ENST00000369413.8 linkuse as main transcript	c.1100C>A	p.Thr367Asn	missense_variant	4/4	1	NM_000862.3	ENSP00000358421	P1
HSD3B1	ENST00000528909.1 linkuse as main transcript	c.1100C>A	p.Thr367Asn	missense_variant	3/3	1		ENSP00000432268	P1

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

GnomAD3 exomes

AF:

0.755

AC:

188429

AN:

249654

Hom.:

72300

AF XY:

0.748

AC XY:

100974

AN XY:

134938

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 SAS exome

AF:

0.810

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

Gnomad4 AFR exome

AF:

0.895

Gnomad4 AMR exome

AF:

0.840

Gnomad4 ASJ exome

AF:

0.670

Gnomad4 EAS exome

AF:

0.939

Gnomad4 SAS exome

AF:

0.808

Gnomad4 FIN exome

AF:

0.742

Gnomad4 NFE exome

AF:

0.677

Gnomad4 OTH exome

AF:

0.718

GnomAD4 genome

AF:

0.764

AC:

115875

AN:

151688

Hom.:

44941

Cov.:

AF XY:

0.771

AC XY:

57102

AN XY:

74092

show subpopulations

Gnomad4 AFR

AF:

0.884

Gnomad4 AMR

AF:

0.789

Gnomad4 ASJ

AF:

0.670

Gnomad4 EAS

AF:

0.924

Gnomad4 SAS

AF:

0.825

Gnomad4 FIN

AF:

0.746

Gnomad4 NFE

AF:

0.677

Gnomad4 OTH

AF:

0.731

Alfa

AF:

0.709

Hom.:

16729

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 14, 2020	This variant is associated with the following publications: (PMID: 31932420) -

Androgen deprivation therapy response

Other:1

drug response, criteria provided, single submitter

clinical testing;research

Desai Sethi Urology Institute, University Of Miami

Mar 01, 2024

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

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

MutationTaster

Benign

1.0

P;P;P

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

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