dbSNP rs2243595: HSD17B3:c.525-199C>T (chr9-96245625-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.525-199C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,188 control chromosomes in the GnomAD database, including 56,939 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.86 ( 56939 hom., cov: 31)

Consequence

HSD17B3
NM_000197.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.830

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 9-96245625-G-A is Benign according to our data. Variant chr9-96245625-G-A is described in ClinVar as Benign. ClinVar VariationId is 1239151.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2 link	c.525-199C>T		intron_variant	Intron 7 of 10	ENST00000375263.8	NP_000188.1	P37058-1Q6FH62
SLC35D2-HSD17B3	NR_182427.1 link	n.3292-199C>T		intron_variant	Intron 22 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8 link	c.525-199C>T		intron_variant	Intron 7 of 10	1	NM_000197.2	ENSP00000364412.3		P37058-1
ENSG00000285269	ENST00000643789.1 link	n.*2201-199C>T		intron_variant	Intron 18 of 21			ENSP00000494818.1		A0A2R8Y5X9

Frequencies

GnomAD3 genomes

AF:

0.864

AC:

131388

AN:

152070

Hom.:

56877

Cov.:

show subpopulations

Gnomad AFR

AF:

0.905

Gnomad AMI

AF:

0.897

Gnomad AMR

AF:

0.849

Gnomad ASJ

AF:

0.831

Gnomad EAS

AF:

0.849

Gnomad SAS

AF:

0.768

Gnomad FIN

AF:

0.912

Gnomad MID

AF:

0.810

Gnomad NFE

AF:

0.845

Gnomad OTH

AF:

0.851

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

GnomAD4 genome

AF:

0.864

AC:

131510

AN:

152188

Hom.:

56939

Cov.:

AF XY:

0.866

AC XY:

64385

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.905

AC:

37574

AN:

41526

American (AMR)

AF:

0.849

AC:

12973

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.831

AC:

2884

AN:

3472

East Asian (EAS)

AF:

0.848

AC:

4377

AN:

5160

South Asian (SAS)

AF:

0.769

AC:

3688

AN:

4796

European-Finnish (FIN)

AF:

0.912

AC:

9667

AN:

10602

Middle Eastern (MID)

AF:

0.813

AC:

239

AN:

294

European-Non Finnish (NFE)

AF:

0.845

AC:

57488

AN:

68024

Other (OTH)

AF:

0.852

AC:

1802

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

936

1872

2808

3744

4680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

896

1792

2688

3584

4480

<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:

0.859

Hom.:

9794

Bravo

AF:

0.861

Asia WGS

AF:

0.813

AC:

2829

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.85

(source)

DANN

Benign

0.35

PhyloP100

-0.83

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