rs16910694

Variant names:

• chr9-96270575-A-C
• rs16910694
• NM_000197.2:c.202-15632T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000197.2(HSD17B3):​c.202-15632T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0235 in 152,378 control chromosomes in the GnomAD database, including 199 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.024 (199 hom., cov: 33)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000285269 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.202-15632T>G		intron_variant	Intron 2 of 10	ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.2969-15632T>G		intron_variant	Intron 17 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.202-15632T>G		intron_variant	Intron 2 of 10	1	NM_000197.2	ENSP00000364412.3
ENSG00000285269	ENST00000643789.1	n.*1878-15632T>G		intron_variant	Intron 13 of 21			ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.0235 AC: 3573 AN: 152260 Hom.: 198 Cov.: 33

Gnomad AFR AF: 0.00475

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.0573

Gnomad SAS AF: 0.0691

Gnomad FIN AF: 0.00555

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00829

Gnomad OTH AF: 0.0244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0235 AC: 3582 AN: 152378 Hom.: 199 Cov.: 33 AF XY: 0.0266 AC XY: 1982 AN XY: 74512

African (AFR) AF: 0.00474 AC: 197 AN: 41600

American (AMR) AF: 0.132 AC: 2020 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

East Asian (EAS) AF: 0.0570 AC: 296 AN: 5190

South Asian (SAS) AF: 0.0690 AC: 333 AN: 4828

European-Finnish (FIN) AF: 0.00555 AC: 59 AN: 10628

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00829 AC: 564 AN: 68036

Other (OTH) AF: 0.0265 AC: 56 AN: 2116

Alfa AF: 0.0277 Hom.: 99

Bravo AF: 0.0314

Asia WGS AF: 0.0750 AC: 260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.63
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16910694; hg19: chr9-99032857;