Genetic Variant HSD17B3:c.154+30dupT (chr9-96301920-C-CA) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000197.2(HSD17B3):c.154+30dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,602,790 control chromosomes in the GnomAD database, including 120,084 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 8036 hom., cov: 19)

Exomes 𝑓: 0.38 ( 112048 hom. )

Consequence

HSD17B3
NM_000197.2 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.71

Publications

2 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: Orphanet, Ambry Genetics, 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 -16 ACMG points.

BP6

Variant 9-96301920-C-CA is Benign according to our data. Variant chr9-96301920-C-CA is described in ClinVar as Benign. ClinVar VariationId is 255508.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2 link	c.154+30dupT		intron_variant	Intron 1 of 10	ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1 link	n.2921+30dupT		intron_variant	Intron 16 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8 link	c.154+30_154+31insT		intron_variant	Intron 1 of 10	1	NM_000197.2	ENSP00000364412.3
ENSG00000285269	ENST00000643789.1 link	n.1830+30_1830+31insT		intron_variant	Intron 12 of 21			ENSP00000494818.1

Frequencies

GnomAD3 genomes

AF:

0.287

AC:

43471

AN:

151546

Hom.:

8039

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0849

Gnomad AMI

AF:

0.553

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.336

Gnomad EAS

AF:

0.0646

Gnomad SAS

AF:

0.173

Gnomad FIN

AF:

0.366

Gnomad MID

AF:

0.220

Gnomad NFE

AF:

0.425

Gnomad OTH

AF:

0.295

GnomAD2 exomes

AF:

0.306

AC:

76738

AN:

250938

AF XY:

0.311

show subpopulations

Gnomad AFR exome

AF:

0.0765

Gnomad AMR exome

AF:

0.215

Gnomad ASJ exome

AF:

0.334

Gnomad EAS exome

AF:

0.0560

Gnomad FIN exome

AF:

0.374

Gnomad NFE exome

AF:

0.422

Gnomad OTH exome

AF:

0.338

GnomAD4 exome

AF:

0.379

AC:

550348

AN:

1451126

Hom.:

112048

Cov.:

AF XY:

0.375

AC XY:

271191

AN XY:

722608

show subpopulations

African (AFR)

AF:

0.0706

AC:

2359

AN:

33416

American (AMR)

AF:

0.216

AC:

9665

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

8715

AN:

26056

East Asian (EAS)

AF:

0.0698

AC:

2769

AN:

39656

South Asian (SAS)

AF:

0.188

AC:

16149

AN:

86126

European-Finnish (FIN)

AF:

0.379

AC:

20213

AN:

53300

Middle Eastern (MID)

AF:

0.256

AC:

1469

AN:

5746

European-Non Finnish (NFE)

AF:

0.425

AC:

468728

AN:

1102076

Other (OTH)

AF:

0.338

AC:

20281

AN:

60040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

15162

30324

45485

60647

75809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13768

27536

41304

55072

68840

<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:

0.287

AC:

43460

AN:

151664

Hom.:

8036

Cov.:

AF XY:

0.278

AC XY:

20600

AN XY:

74034

show subpopulations

African (AFR)

AF:

0.0846

AC:

3505

AN:

41408

American (AMR)

AF:

0.247

AC:

3757

AN:

15208

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

1165

AN:

3464

East Asian (EAS)

AF:

0.0645

AC:

332

AN:

5144

South Asian (SAS)

AF:

0.173

AC:

832

AN:

4800

European-Finnish (FIN)

AF:

0.366

AC:

3830

AN:

10454

Middle Eastern (MID)

AF:

0.205

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.425

AC:

28869

AN:

67894

Other (OTH)

AF:

0.291

AC:

611

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1367

2734

4100

5467

6834

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<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:

0.317

Hom.:

1826

Bravo

AF:

0.266

Asia WGS

AF:

0.109

AC:

379

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.7

Mutation Taster

=100/0

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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9-96301920-CA-CAA

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