Genetic Variant HSD17B3:c.154+30dupT (chr9-96301920-C-CA) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_000197.2(HSD17B3):c.154+30dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,602,790 control chromosomes in the GnomAD database, including 120,084 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 8036 hom., cov: 19)

Exomes 𝑓: 0.38 ( 112048 hom. )

Consequence

HSD17B3
NM_000197.2 intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 1.71

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 -16 ACMG points.

BP6

Variant 9-96301920-C-CA is Benign according to our data. Variant chr9-96301920-C-CA is described in ClinVar as [Benign]. Clinvar id is 255508.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2 link	c.154+30dupT		intron_variant	Intron 1 of 10	ENST00000375263.8	NP_000188.1	P37058-1Q6FH62
SLC35D2-HSD17B3	NR_182427.1 link	n.2921+30dupT		intron_variant	Intron 16 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8 link	c.154+30_154+31insT		intron_variant	Intron 1 of 10	1	NM_000197.2	ENSP00000364412.3		P37058-1
ENSG00000285269	ENST00000643789.1 link	n.1830+30_1830+31insT		intron_variant	Intron 12 of 21			ENSP00000494818.1		A0A2R8Y5X9

Frequencies

GnomAD3 genomes

AF:

0.287

AC:

43471

AN:

151546

Hom.:

8039

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0849

Gnomad AMI

AF:

0.553

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.336

Gnomad EAS

AF:

0.0646

Gnomad SAS

AF:

0.173

Gnomad FIN

AF:

0.366

Gnomad MID

AF:

0.220

Gnomad NFE

AF:

0.425

Gnomad OTH

AF:

0.295

GnomAD3 exomes

AF:

0.306

AC:

76738

AN:

250938

Hom.:

13993

AF XY:

0.311

AC XY:

42198

AN XY:

135650

show subpopulations

Gnomad AFR exome

AF:

0.0765

Gnomad AMR exome

AF:

0.215

Gnomad ASJ exome

AF:

0.334

Gnomad EAS exome

AF:

0.0560

Gnomad SAS exome

AF:

0.185

Gnomad FIN exome

AF:

0.374

Gnomad NFE exome

AF:

0.422

Gnomad OTH exome

AF:

0.338

GnomAD4 exome

AF:

0.379

AC:

550348

AN:

1451126

Hom.:

112048

Cov.:

AF XY:

0.375

AC XY:

271191

AN XY:

722608

show subpopulations

Gnomad4 AFR exome

AF:

0.0706

Gnomad4 AMR exome

AF:

0.216

Gnomad4 ASJ exome

AF:

0.334

Gnomad4 EAS exome

AF:

0.0698

Gnomad4 SAS exome

AF:

0.188

Gnomad4 FIN exome

AF:

0.379

Gnomad4 NFE exome

AF:

0.425

Gnomad4 OTH exome

AF:

0.338

GnomAD4 genome

AF:

0.287

AC:

43460

AN:

151664

Hom.:

8036

Cov.:

AF XY:

0.278

AC XY:

20600

AN XY:

74034

show subpopulations

Gnomad4 AFR

AF:

0.0846

Gnomad4 AMR

AF:

0.247

Gnomad4 ASJ

AF:

0.336

Gnomad4 EAS

AF:

0.0645

Gnomad4 SAS

AF:

0.173

Gnomad4 FIN

AF:

0.366

Gnomad4 NFE

AF:

0.425

Gnomad4 OTH

AF:

0.291

Bravo

AF:

0.266

Asia WGS

AF:

0.109

AC:

379

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

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.

9-96301920-CA-CAA

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