rs8190498

Variant names:

• chr9-96298913-C-A
• rs8190498
• NM_000197.2:c.155-451G>T

Variant summary

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

The NM_000197.2(HSD17B3):​c.155-451G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 151,934 control chromosomes in the GnomAD database, including 6,258 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 0.27 (6258 hom., cov: 31)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.155-451G>T		intron_variant	Intron 1 of 10	ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.2922-451G>T		intron_variant	Intron 16 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.155-451G>T		intron_variant	Intron 1 of 10	1	NM_000197.2	ENSP00000364412.3
ENSG00000285269	ENST00000643789.1	n.*1831-451G>T		intron_variant	Intron 12 of 21			ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41359 AN: 151816 Hom.: 6258 Cov.: 31

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.0618

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.272 AC: 41366 AN: 151934 Hom.: 6258 Cov.: 31 AF XY: 0.265 AC XY: 19658 AN XY: 74238

African (AFR) AF: 0.183 AC: 7585 AN: 41444

American (AMR) AF: 0.228 AC: 3476 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1053 AN: 3470

East Asian (EAS) AF: 0.0617 AC: 319 AN: 5168

South Asian (SAS) AF: 0.123 AC: 591 AN: 4808

European-Finnish (FIN) AF: 0.314 AC: 3308 AN: 10548

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23913 AN: 67940

Other (OTH) AF: 0.269 AC: 566 AN: 2108

Alfa AF: 0.315 Hom.: 1069

Bravo AF: 0.262

Asia WGS AF: 0.0930 AC: 326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.42
PhyloP100		-0.0050
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: rs8190498; hg19: chr9-99061195;