Variant rs2066474 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.-39A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,606,212 control chromosomes in the GnomAD database, including 36,679 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3510 hom., cov: 31)

Exomes 𝑓: 0.20 ( 33169 hom. )

Consequence

HSD17B3
NM_000197.2 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.252

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=-0.89).

BP6

Variant 9-96302143-T-C is Benign according to our data. Variant chr9-96302143-T-C is described in ClinVar as [Benign]. Clinvar id is 255507.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B3	NM_000197.2 linkuse as main transcript	c.-39A>G		5_prime_UTR_variant	1/11	ENST00000375263.8
SLC35D2-HSD17B3	NR_182427.1 linkuse as main transcript	n.2729A>G		non_coding_transcript_exon_variant	16/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B3	ENST00000375263.8 linkuse as main transcript	c.-39A>G		5_prime_UTR_variant	1/11	1	NM_000197.2	P1	P37058-1

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

31172

AN:

151904

Hom.:

3511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.474

Gnomad SAS

AF:

0.369

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.207

GnomAD3 exomes

AF:

0.253

AC:

60253

AN:

238376

Hom.:

8745

AF XY:

0.255

AC XY:

32845

AN XY:

128738

show subpopulations

Gnomad AFR exome

AF:

0.172

Gnomad AMR exome

AF:

0.276

Gnomad ASJ exome

AF:

0.253

Gnomad EAS exome

AF:

0.502

Gnomad SAS exome

AF:

0.380

Gnomad FIN exome

AF:

0.255

Gnomad NFE exome

AF:

0.182

Gnomad OTH exome

AF:

0.225

GnomAD4 exome

AF:

0.201

AC:

292802

AN:

1454190

Hom.:

33169

Cov.:

AF XY:

0.207

AC XY:

149299

AN XY:

722948

show subpopulations

Gnomad4 AFR exome

AF:

0.178

Gnomad4 AMR exome

AF:

0.269

Gnomad4 ASJ exome

AF:

0.256

Gnomad4 EAS exome

AF:

0.457

Gnomad4 SAS exome

AF:

0.373

Gnomad4 FIN exome

AF:

0.254

Gnomad4 NFE exome

AF:

0.172

Gnomad4 OTH exome

AF:

0.220

GnomAD4 genome

AF:

0.205

AC:

31199

AN:

152022

Hom.:

3510

Cov.:

AF XY:

0.214

AC XY:

15882

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.171

Gnomad4 AMR

AF:

0.238

Gnomad4 ASJ

AF:

0.241

Gnomad4 EAS

AF:

0.473

Gnomad4 SAS

AF:

0.368

Gnomad4 FIN

AF:

0.256

Gnomad4 NFE

AF:

0.177

Gnomad4 OTH

AF:

0.206

Alfa

AF:

0.191

Hom.:

1430

Bravo

AF:

0.203

Asia WGS

AF:

0.362

AC:

1258

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 25, 2018	- -
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

- -

Testosterone 17-beta-dehydrogenase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.7

DANN

Benign

0.63

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