rs2066479

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_000197.2(HSD17B3):c.865G>A(p.Gly289Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 1,613,652 control chromosomes in the GnomAD database, including 4,380 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.077 ( 652 hom., cov: 33)

Exomes 𝑓: 0.060 ( 3728 hom. )

Consequence

HSD17B3
NM_000197.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.410

Publications

47 publications found

Variant links:

Genes affected

HSD17B3 (HGNC:5212): (hydroxysteroid 17-beta dehydrogenase 3) This isoform of 17 beta-hydroxysteroid dehydrogenase is expressed predominantly in the testis and catalyzes the conversion of androstenedione to testosterone. It preferentially uses NADP as cofactor. Deficiency can result in male pseudohermaphroditism with gynecomastia. [provided by RefSeq, Jul 2008]

HSD17B3 Gene-Disease associations (from GenCC):

46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

HSD17B3 links:

ENSG00000285269 (HGNC:):

ENSG00000285269 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=0.002269566).

BP6

Variant 9-96235528-C-T is Benign according to our data. Variant chr9-96235528-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 255511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000197.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	NM_000197.2	MANE Select	c.865G>A	p.Gly289Ser	missense	Exon 11 of 11	NP_000188.1	P37058-1
	SLC35D2-HSD17B3	NR_182427.1		n.3632G>A		non_coding_transcript_exon	Exon 26 of 26

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HSD17B3	ENST00000375263.8	TSL:1 MANE Select	c.865G>A	p.Gly289Ser	missense	Exon 11 of 11	ENSP00000364412.3	P37058-1
HSD17B3	ENST00000375262.4	TSL:1	c.715G>A	p.Gly239Ser	missense	Exon 10 of 10	ENSP00000364411.2	P37058-2
ENSG00000285269	ENST00000643789.1		n.*2541G>A		non_coding_transcript_exon	Exon 22 of 22	ENSP00000494818.1	A0A2R8Y5X9

Frequencies

GnomAD3 genomes

AF:

0.0775

AC:

11786

AN:

152124

Hom.:

653

Cov.:

show subpopulations

Gnomad AFR

AF:

0.113

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.0584

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.0771

Gnomad FIN

AF:

0.0464

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0498

Gnomad OTH

AF:

0.0847

GnomAD2 exomes

AF:

0.0724

AC:

18153

AN:

250766

AF XY:

0.0712

show subpopulations

Gnomad AFR exome

AF:

0.110

Gnomad AMR exome

AF:

0.0489

Gnomad ASJ exome

AF:

0.124

Gnomad EAS exome

AF:

0.228

Gnomad FIN exome

AF:

0.0417

Gnomad NFE exome

AF:

0.0495

Gnomad OTH exome

AF:

0.0659

GnomAD4 exome

AF:

0.0602

AC:

87913

AN:

1461410

Hom.:

3728

Cov.:

AF XY:

0.0607

AC XY:

44142

AN XY:

726984

show subpopulations

African (AFR)

AF:

0.113

AC:

3774

AN:

33474

American (AMR)

AF:

0.0493

AC:

2202

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.128

AC:

3352

AN:

26128

East Asian (EAS)

AF:

0.239

AC:

9493

AN:

39676

South Asian (SAS)

AF:

0.0747

AC:

6438

AN:

86198

European-Finnish (FIN)

AF:

0.0416

AC:

2219

AN:

53368

Middle Eastern (MID)

AF:

0.0529

AC:

305

AN:

5766

European-Non Finnish (NFE)

AF:

0.0500

AC:

55571

AN:

1111722

Other (OTH)

AF:

0.0755

AC:

4559

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

4348

8696

13043

17391

21739

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2284

4568

6852

9136

11420

<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:

0.0774

AC:

11788

AN:

152242

Hom.:

652

Cov.:

AF XY:

0.0778

AC XY:

5794

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.113

AC:

4699

AN:

41536

American (AMR)

AF:

0.0581

AC:

889

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.123

AC:

427

AN:

3472

East Asian (EAS)

AF:

0.239

AC:

1237

AN:

5180

South Asian (SAS)

AF:

0.0769

AC:

371

AN:

4824

European-Finnish (FIN)

AF:

0.0464

AC:

492

AN:

10596

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0498

AC:

3386

AN:

68020

Other (OTH)

AF:

0.0833

AC:

176

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

541

1082

1624

2165

2706

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

256

384

512

640

<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:

0.0644

Hom.:

1377

Bravo

AF:

0.0815

Asia WGS

AF:

0.146

AC:

512

AN:

3478

EpiCase

AF:

0.0546

EpiControl

AF:

0.0591

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (3)

Testosterone 17-beta-dehydrogenase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

1.4

(source)

DANN

Benign

0.74

DEOGEN2

Benign

0.070

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00093

LIST_S2

Benign

0.30

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.9

PhyloP100

-0.41

PrimateAI

Benign

0.25

PROVEAN

Benign

1.1

REVEL

Benign

0.15

Sift

Benign

0.81

Sift4G

Benign

0.81

Varity_R

0.024

gMVP

0.47

Mutation Taster

=99/1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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