Genetic Variant NM_000197.2:c.453+803T>C (chr9-96250615-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000197.2(HSD17B3):c.453+803T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 326,016 control chromosomes in the GnomAD database, including 12,772 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.28 ( 6448 hom., cov: 31)

Exomes 𝑓: 0.26 ( 6324 hom. )

Consequence

HSD17B3
NM_000197.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.66

Publications

3 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 links:

ENSG00000285269 (HGNC:):

ENSG00000285269 links:

HSD17B3-AS1 (HGNC:53136): (HSD17B3 antisense RNA 1)

HSD17B3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2 link	c.453+803T>C		intron_variant	Intron 5 of 10	ENST00000375263.8	NP_000188.1	P37058-1Q6FH62
SLC35D2-HSD17B3	NR_182427.1 link	n.3220+803T>C		intron_variant	Intron 20 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8 link	c.453+803T>C		intron_variant	Intron 5 of 10	1	NM_000197.2	ENSP00000364412.3		P37058-1
ENSG00000285269	ENST00000643789.1 link	n.*2129+803T>C		intron_variant	Intron 16 of 21			ENSP00000494818.1		A0A2R8Y5X9

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42578

AN:

151826

Hom.:

6435

Cov.:

show subpopulations

Gnomad AFR

AF:

0.367

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.280

Gnomad EAS

AF:

0.0285

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.284

Gnomad MID

AF:

0.325

Gnomad NFE

AF:

0.272

Gnomad OTH

AF:

0.269

GnomAD4 exome

AF:

0.261

AC:

45411

AN:

174072

Hom.:

6324

AF XY:

0.260

AC XY:

21500

AN XY:

82546

show subpopulations

African (AFR)

AF:

0.389

AC:

1385

AN:

3562

American (AMR)

AF:

0.185

AC:

153

AN:

826

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

752

AN:

2728

East Asian (EAS)

AF:

0.0180

AC:

118

AN:

6540

South Asian (SAS)

AF:

0.138

AC:

425

AN:

3090

European-Finnish (FIN)

AF:

0.340

AC:

AN:

Middle Eastern (MID)

AF:

0.280

AC:

135

AN:

482

European-Non Finnish (NFE)

AF:

0.271

AC:

40643

AN:

149788

Other (OTH)

AF:

0.254

AC:

1783

AN:

7006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1645

3289

4934

6578

8223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1656

3312

4968

6624

8280

<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:

0.281

AC:

42626

AN:

151944

Hom.:

6448

Cov.:

AF XY:

0.274

AC XY:

20320

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.367

AC:

15197

AN:

41380

American (AMR)

AF:

0.211

AC:

3218

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.280

AC:

971

AN:

3468

East Asian (EAS)

AF:

0.0286

AC:

148

AN:

5176

South Asian (SAS)

AF:

0.138

AC:

663

AN:

4818

European-Finnish (FIN)

AF:

0.284

AC:

3000

AN:

10566

Middle Eastern (MID)

AF:

0.329

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.272

AC:

18484

AN:

67952

Other (OTH)

AF:

0.269

AC:

568

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1504

3008

4512

6016

7520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<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:

0.279

Hom.:

824

Bravo

AF:

0.280

Asia WGS

AF:

0.114

AC:

396

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.031

(source)

DANN

Benign

0.093

PhyloP100

-2.7

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over