Genetic Variant HSD17B3:c.673-75G>A (chr9-96240982-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000197.2(HSD17B3):c.673-75G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 1,549,094 control chromosomes in the GnomAD database, including 556,398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 59627 hom., cov: 31)

Exomes 𝑓: 0.84 ( 496771 hom. )

Consequence

HSD17B3
NM_000197.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.63

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 9-96240982-C-T is Benign according to our data. Variant chr9-96240982-C-T is described in ClinVar as [Benign]. Clinvar id is 1291003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2 link	c.673-75G>A		intron_variant	Intron 9 of 10	ENST00000375263.8	NP_000188.1	P37058-1Q6FH62
SLC35D2-HSD17B3	NR_182427.1 link	n.3440-75G>A		intron_variant	Intron 24 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8 link	c.673-75G>A		intron_variant	Intron 9 of 10	1	NM_000197.2	ENSP00000364412.3		P37058-1
ENSG00000285269	ENST00000643789.1 link	n.*2349-75G>A		intron_variant	Intron 20 of 21			ENSP00000494818.1		A0A2R8Y5X9

Frequencies

GnomAD3 genomes

AF:

0.883

AC:

134252

AN:

152042

Hom.:

59563

Cov.:

show subpopulations

Gnomad AFR

AF:

0.970

Gnomad AMI

AF:

0.902

Gnomad AMR

AF:

0.857

Gnomad ASJ

AF:

0.831

Gnomad EAS

AF:

0.849

Gnomad SAS

AF:

0.769

Gnomad FIN

AF:

0.910

Gnomad MID

AF:

0.823

Gnomad NFE

AF:

0.845

Gnomad OTH

AF:

0.865

GnomAD4 exome

AF:

0.842

AC:

1176903

AN:

1396934

Hom.:

496771

AF XY:

0.841

AC XY:

587189

AN XY:

698312

show subpopulations

Gnomad4 AFR exome

AF:

0.976

Gnomad4 AMR exome

AF:

0.816

Gnomad4 ASJ exome

AF:

0.840

Gnomad4 EAS exome

AF:

0.849

Gnomad4 SAS exome

AF:

0.777

Gnomad4 FIN exome

AF:

0.906

Gnomad4 NFE exome

AF:

0.841

Gnomad4 OTH exome

AF:

0.849

GnomAD4 genome

AF:

0.883

AC:

134376

AN:

152160

Hom.:

59627

Cov.:

AF XY:

0.884

AC XY:

65726

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.970

Gnomad4 AMR

AF:

0.857

Gnomad4 ASJ

AF:

0.831

Gnomad4 EAS

AF:

0.848

Gnomad4 SAS

AF:

0.770

Gnomad4 FIN

AF:

0.910

Gnomad4 NFE

AF:

0.845

Gnomad4 OTH

AF:

0.866

Alfa

AF:

0.877

Hom.:

7344

Bravo

AF:

0.884

Asia WGS

AF:

0.818

AC:

2847

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

-0.99

CADD

Benign

0.36

DANN

Benign

0.61

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over