9-96302014-C-T

Position:

chr9-96302014-C-T

Variant summary

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

The NM_000197.2(HSD17B3):c.91G>A(p.Val31Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,614,124 control chromosomes in the GnomAD database, including 352 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 29 hom., cov: 31)

Exomes 𝑓: 0.012 ( 323 hom. )

Consequence

HSD17B3
NM_000197.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.34

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:

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 (MetaRNN=0.0019617677).

BP6

Variant 9-96302014-C-T is Benign according to our data. Variant chr9-96302014-C-T is described in ClinVar as [Benign]. Clinvar id is 367684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-96302014-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B3	NM_000197.2 link	c.91G>A	p.Val31Ile	missense_variant	1/11	ENST00000375263.8	NP_000188.1	P37058-1Q6FH62
SLC35D2-HSD17B3	NR_182427.1 link	n.2858G>A		non_coding_transcript_exon_variant	16/26

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HSD17B3	ENST00000375263.8 link	c.91G>A	p.Val31Ile	missense_variant	1/11	1	NM_000197.2	ENSP00000364412.3	P37058-1
ENSG00000285269	ENST00000643789.1 link	n.*1767G>A		non_coding_transcript_exon_variant	12/22			ENSP00000494818.1	A0A2R8Y5X9
ENSG00000285269	ENST00000643789.1 link	n.*1767G>A		3_prime_UTR_variant	12/22			ENSP00000494818.1	A0A2R8Y5X9

Frequencies

GnomAD3 genomes

AF:

0.0121

AC:

1838

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0121

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.00897

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.0566

Gnomad SAS

AF:

0.0615

Gnomad FIN

AF:

0.00461

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00727

Gnomad OTH

AF:

0.0119

GnomAD3 exomes

AF:

0.0177

AC:

4457

AN:

251448

Hom.:

128

AF XY:

0.0193

AC XY:

2628

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.0119

Gnomad AMR exome

AF:

0.00431

Gnomad ASJ exome

AF:

0.00397

Gnomad EAS exome

AF:

0.0644

Gnomad SAS exome

AF:

0.0600

Gnomad FIN exome

AF:

0.00522

Gnomad NFE exome

AF:

0.00753

Gnomad OTH exome

AF:

0.0135

GnomAD4 exome

AF:

0.0118

AC:

17210

AN:

1461842

Hom.:

323

Cov.:

AF XY:

0.0132

AC XY:

9617

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0109

Gnomad4 AMR exome

AF:

0.00537

Gnomad4 ASJ exome

AF:

0.00386

Gnomad4 EAS exome

AF:

0.0538

Gnomad4 SAS exome

AF:

0.0600

Gnomad4 FIN exome

AF:

0.00616

Gnomad4 NFE exome

AF:

0.00716

Gnomad4 OTH exome

AF:

0.0143

GnomAD4 genome

AF:

0.0121

AC:

1842

AN:

152282

Hom.:

Cov.:

AF XY:

0.0128

AC XY:

956

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0122

Gnomad4 AMR

AF:

0.00895

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.0567

Gnomad4 SAS

AF:

0.0612

Gnomad4 FIN

AF:

0.00461

Gnomad4 NFE

AF:

0.00728

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00918

Hom.:

Bravo

AF:

0.0119

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.00908

AC:

ESP6500EA

AF:

0.00767

AC:

ExAC

AF:

0.0190

AC:

2309

Asia WGS

AF:

0.0580

AC:

201

AN:

3478

EpiCase

AF:

0.00671

EpiControl

AF:

0.00717

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -

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

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.49

DANN

Benign

0.25

DEOGEN2

Benign

0.081

T;.;.;T

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.0024

LIST_S2

Benign

0.32

T;T;T;T

MetaRNN

Benign

0.0020

T;T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

-1.1

N;N;.;.

PrimateAI

Benign

0.32

PROVEAN

Benign

0.10

N;N;.;.

REVEL

Benign

0.20

Sift

Benign

1.0

T;T;.;.

Sift4G

Benign

0.84

T;T;.;.

Polyphen

0.0

B;.;.;.

Vest4

0.033

MPC

0.13

ClinPred

0.0011

GERP RS

-9.6

Varity_R

0.018

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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