dbSNP rs8190557: HSD17B3:c.822+186C>T (chr9-96240572-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000197.2(HSD17B3):c.822+186C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,032 control chromosomes in the GnomAD database, including 1,984 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.13 ( 1984 hom., cov: 32)

Consequence

HSD17B3
NM_000197.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.49

Publications

4 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 9-96240572-G-A is Benign according to our data. Variant chr9-96240572-G-A is described in ClinVar as Benign. ClinVar VariationId is 1253389.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2 link	c.822+186C>T		intron_variant	Intron 10 of 10	ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1 link	n.3589+186C>T		intron_variant	Intron 25 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8 link	c.822+186C>T		intron_variant	Intron 10 of 10	1	NM_000197.2	ENSP00000364412.3
ENSG00000285269	ENST00000643789.1 link	n.*2498+186C>T		intron_variant	Intron 21 of 21			ENSP00000494818.1

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

19999

AN:

151914

Hom.:

1971

Cov.:

show subpopulations

Gnomad AFR

AF:

0.265

Gnomad AMI

AF:

0.0861

Gnomad AMR

AF:

0.0811

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.0817

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.0637

Gnomad OTH

AF:

0.127

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.132

AC:

20040

AN:

152032

Hom.:

1984

Cov.:

AF XY:

0.133

AC XY:

9899

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.266

AC:

11016

AN:

41448

American (AMR)

AF:

0.0808

AC:

1235

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

457

AN:

3466

East Asian (EAS)

AF:

0.239

AC:

1227

AN:

5142

South Asian (SAS)

AF:

0.109

AC:

525

AN:

4808

European-Finnish (FIN)

AF:

0.0817

AC:

866

AN:

10594

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0637

AC:

4332

AN:

67988

Other (OTH)

AF:

0.125

AC:

263

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

806

1611

2417

3222

4028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

206

412

618

824

1030

<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:

0.100

Hom.:

272

Bravo

AF:

0.139

Asia WGS

AF:

0.173

AC:

605

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 30, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.023

(source)

DANN

Benign

0.51

PhyloP100

-1.5

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over