rs2066480

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.91G>A(p.Val31Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,614,124 control chromosomes in the GnomAD database, including 352 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 Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 29 hom., cov: 31)

Exomes 𝑓: 0.012 ( 323 hom. )

Consequence

HSD17B3
NM_000197.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.34

Publications

19 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

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=0.0019617677).

BP6

Variant 9-96302014-C-T is Benign according to our data. Variant chr9-96302014-C-T is described in ClinVar as Benign. ClinVar VariationId is 367684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0554 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.91G>A	p.Val31Ile	missense	Exon 1 of 11	NP_000188.1	P37058-1
	SLC35D2-HSD17B3	NR_182427.1		n.2858G>A		non_coding_transcript_exon	Exon 16 of 26

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HSD17B3	ENST00000375263.8	TSL:1 MANE Select	c.91G>A	p.Val31Ile	missense	Exon 1 of 11	ENSP00000364412.3	P37058-1
HSD17B3	ENST00000375262.4	TSL:1	c.91G>A	p.Val31Ile	missense	Exon 1 of 10	ENSP00000364411.2	P37058-2
ENSG00000285269	ENST00000643789.1		n.*1767G>A		non_coding_transcript_exon	Exon 12 of 22	ENSP00000494818.1	A0A2R8Y5X9

Frequencies

GnomAD3 genomes

AF:

0.0121

AC:

1838

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0121

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.00897

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.0566

Gnomad SAS

AF:

0.0615

Gnomad FIN

AF:

0.00461

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00727

Gnomad OTH

AF:

0.0119

GnomAD2 exomes

AF:

0.0177

AC:

4457

AN:

251448

AF XY:

0.0193

show subpopulations

Gnomad AFR exome

AF:

0.0119

Gnomad AMR exome

AF:

0.00431

Gnomad ASJ exome

AF:

0.00397

Gnomad EAS exome

AF:

0.0644

Gnomad FIN exome

AF:

0.00522

Gnomad NFE exome

AF:

0.00753

Gnomad OTH exome

AF:

0.0135

GnomAD4 exome

AF:

0.0118

AC:

17210

AN:

1461842

Hom.:

323

Cov.:

AF XY:

0.0132

AC XY:

9617

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.0109

AC:

366

AN:

33480

American (AMR)

AF:

0.00537

AC:

240

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00386

AC:

101

AN:

26136

East Asian (EAS)

AF:

0.0538

AC:

2137

AN:

39696

South Asian (SAS)

AF:

0.0600

AC:

5175

AN:

86252

European-Finnish (FIN)

AF:

0.00616

AC:

329

AN:

53420

Middle Eastern (MID)

AF:

0.00589

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00716

AC:

7964

AN:

1111974

Other (OTH)

AF:

0.0143

AC:

864

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

944

1888

2831

3775

4719

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

390

780

1170

1560

1950

<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:

0.0121

AC:

1842

AN:

152282

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

956

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0122

AC:

507

AN:

41544

American (AMR)

AF:

0.00895

AC:

137

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3470

East Asian (EAS)

AF:

0.0567

AC:

293

AN:

5164

South Asian (SAS)

AF:

0.0612

AC:

295

AN:

4822

European-Finnish (FIN)

AF:

0.00461

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00728

AC:

495

AN:

68040

Other (OTH)

AF:

0.0128

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

174

260

347

434

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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:

0.00986

Hom.:

Bravo

AF:

0.0119

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.00908

AC:

ESP6500EA

AF:

0.00767

AC:

ExAC

AF:

0.0190

AC:

2309

Asia WGS

AF:

0.0580

AC:

201

AN:

3478

EpiCase

AF:

0.00671

EpiControl

AF:

0.00717

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Testosterone 17-beta-dehydrogenase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.49

(source)

DANN

Benign

0.25

DEOGEN2

Benign

0.081

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.32

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.76

MutationAssessor

Benign

-1.1

PhyloP100

-1.3

PrimateAI

Benign

0.32

PROVEAN

Benign

0.10

REVEL

Benign

0.20

Sift

Benign

1.0

Sift4G

Benign

0.84

Polyphen

0.0

Vest4

0.033

MPC

0.13

ClinPred

0.0011

GERP RS

-9.6

PromoterAI

0.0056

Neutral

(source)

Varity_R

0.018

gMVP

0.35

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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