chr1-119422310-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000198.4(HSD3B2):c.809T>C(p.Ile270Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000701 in 1,614,118 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. I270I) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00073 ( 1 hom. )

Consequence

HSD3B2
NM_000198.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:7B:1

Conservation

PhyloP100: -0.571

Publications

3 publications found

Variant links:

Genes affected

HSD3B2 (HGNC:5218): (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2) The protein encoded by this gene is a bifunctional enzyme that catalyzes the oxidative conversion of delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. It plays a crucial role in the biosynthesis of all classes of hormonal steroids. This gene is predominantly expressed in the adrenals and the gonads. Mutations in this gene are associated with 3-beta-hydroxysteroid dehydrogenase, type II, deficiency. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2009]

HSD3B2 Gene-Disease associations (from GenCC):

congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

HSD3B2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026067734).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000198.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD3B2	NM_000198.4	MANE Select	c.809T>C	p.Ile270Thr	missense	Exon 4 of 4	NP_000189.1
	HSD3B2	NM_001166120.2		c.809T>C	p.Ile270Thr	missense	Exon 4 of 4	NP_001159592.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
HSD3B2	ENST00000369416.4	TSL:1 MANE Select	c.809T>C	p.Ile270Thr	missense	Exon 4 of 4	ENSP00000358424.3
HSD3B2	ENST00000543831.5	TSL:3	c.809T>C	p.Ile270Thr	missense	Exon 4 of 4	ENSP00000445122.1
HSD3B2	ENST00000902254.1		c.809T>C	p.Ile270Thr	missense	Exon 3 of 3	ENSP00000572313.1

Frequencies

GnomAD3 genomes

AF:

0.000401

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000764

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000458

AC:

115

AN:

251256

AF XY:

0.000427

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000907

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000732

AC:

1070

AN:

1461828

Hom.:

Cov.:

AF XY:

0.000714

AC XY:

519

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33478

American (AMR)

AF:

0.0000224

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000536

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000918

AC:

1021

AN:

1111976

Other (OTH)

AF:

0.000464

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

156

235

313

391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<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:

0.000401

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41562

American (AMR)

AF:

0.000131

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000764

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000545

Hom.:

Bravo

AF:

0.000385

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000354

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000652

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

3 beta-Hydroxysteroid dehydrogenase deficiency (3)

not provided (3)

HSD3B2-related disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.46

CADD

Benign

0.0010

(source)

DANN

Benign

0.17

DEOGEN2

Benign

0.27

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.011

M_CAP

Benign

0.017

MetaRNN

Benign

0.026

MetaSVM

Benign

-0.81

MutationAssessor

Benign

-1.3

PhyloP100

-0.57

PrimateAI

Benign

0.26

PROVEAN

Benign

1.8

REVEL

Benign

0.22

Sift

Benign

1.0

Sift4G

Benign

0.64

Polyphen

0.0

Vest4

0.27

MVP

0.83

MPC

0.32

ClinPred

0.010

GERP RS

-8.0

Varity_R

0.025

gMVP

0.32

Mutation Taster

=72/28

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over