Variant 9-96251381-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000197.2(HSD17B3):c.453+37T>C 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 1,584,216 control chromosomes in the GnomAD database, including 568,629 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 59222 hom., cov: 32)

Exomes 𝑓: 0.84 ( 509407 hom. )

Consequence

HSD17B3
NM_000197.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.53

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:

SLC35D2-HSD17B3 (HGNC:):

SLC35D2-HSD17B3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 9-96251381-A-G is Benign according to our data. Variant chr9-96251381-A-G is described in ClinVar as [Benign]. Clinvar id is 255509.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B3	NM_000197.2 linkuse as main transcript	c.453+37T>C		intron_variant		ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1 linkuse as main transcript	n.3220+37T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8 linkuse as main transcript	c.453+37T>C		intron_variant		1	NM_000197.2	ENSP00000364412	P1	P37058-1

Frequencies

GnomAD3 genomes

AF:

0.880

AC:

133873

AN:

152122

Hom.:

59160

Cov.:

show subpopulations

Gnomad AFR

AF:

0.959

Gnomad AMI

AF:

0.904

Gnomad AMR

AF:

0.856

Gnomad ASJ

AF:

0.832

Gnomad EAS

AF:

0.850

Gnomad SAS

AF:

0.771

Gnomad FIN

AF:

0.910

Gnomad MID

AF:

0.816

Gnomad NFE

AF:

0.845

Gnomad OTH

AF:

0.866

GnomAD3 exomes

AF:

0.844

AC:

211833

AN:

250888

Hom.:

89813

AF XY:

0.840

AC XY:

113854

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.962

Gnomad AMR exome

AF:

0.810

Gnomad ASJ exome

AF:

0.838

Gnomad EAS exome

AF:

0.847

Gnomad SAS exome

AF:

0.774

Gnomad FIN exome

AF:

0.904

Gnomad NFE exome

AF:

0.845

Gnomad OTH exome

AF:

0.847

GnomAD4 exome

AF:

0.843

AC:

1206649

AN:

1431976

Hom.:

509407

Cov.:

AF XY:

0.841

AC XY:

600795

AN XY:

714308

show subpopulations

Gnomad4 AFR exome

AF:

0.966

Gnomad4 AMR exome

AF:

0.815

Gnomad4 ASJ exome

AF:

0.840

Gnomad4 EAS exome

AF:

0.849

Gnomad4 SAS exome

AF:

0.778

Gnomad4 FIN exome

AF:

0.906

Gnomad4 NFE exome

AF:

0.842

Gnomad4 OTH exome

AF:

0.848

GnomAD4 genome

AF:

0.880

AC:

133995

AN:

152240

Hom.:

59222

Cov.:

AF XY:

0.881

AC XY:

65561

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.959

Gnomad4 AMR

AF:

0.856

Gnomad4 ASJ

AF:

0.832

Gnomad4 EAS

AF:

0.849

Gnomad4 SAS

AF:

0.771

Gnomad4 FIN

AF:

0.910

Gnomad4 NFE

AF:

0.845

Gnomad4 OTH

AF:

0.867

Alfa

AF:

0.850

Hom.:

27914

Bravo

AF:

0.880

Asia WGS

AF:

0.819

AC:

2849

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.40

DANN

Benign

0.34

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