rs729390

Variant names:

• chr9-96250246-C-T
• rs729390
• NM_000197.2:c.454-460G>A

Variant summary

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

The NM_000197.2(HSD17B3):​c.454-460G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 1,111,484 control chromosomes in the GnomAD database, including 40,724 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 (6064 hom., cov: 31)
  • Exomes 𝑓: 0.26 (34660 hom.)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 2 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]

ENSG00000285269 (HGNC:):

HSD17B3-AS1 (HGNC:53136): (HSD17B3 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.454-460G>A		intron_variant	Intron 5 of 10	ENST00000375263.8	NP_000188.1
HSD17B3-AS1	NR_146524.1	n.924C>T		non_coding_transcript_exon_variant	Exon 3 of 3
SLC35D2-HSD17B3	NR_182427.1	n.3221-460G>A		intron_variant	Intron 20 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.454-460G>A		intron_variant	Intron 5 of 10	1	NM_000197.2	ENSP00000364412.3
ENSG00000285269	ENST00000643789.1	n.*2130-460G>A		intron_variant	Intron 16 of 21			ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41495 AN: 151876 Hom.: 6055 Cov.: 31

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.0284

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.262

GnomAD4 exome AF: 0.264 AC: 253117 AN: 959490 Hom.: 34660 Cov.: 24 AF XY: 0.263 AC XY: 117288 AN XY: 446026

African (AFR) AF: 0.361 AC: 7848 AN: 21724

American (AMR) AF: 0.170 AC: 1219 AN: 7174

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 3216 AN: 11370

East Asian (EAS) AF: 0.0210 AC: 394 AN: 18774

South Asian (SAS) AF: 0.137 AC: 3001 AN: 21836

European-Finnish (FIN) AF: 0.265 AC: 448 AN: 1690

Middle Eastern (MID) AF: 0.307 AC: 696 AN: 2264

European-Non Finnish (NFE) AF: 0.271 AC: 227382 AN: 838378

Other (OTH) AF: 0.246 AC: 8913 AN: 36280

GnomAD4 genome AF: 0.273 AC: 41538 AN: 151994 Hom.: 6064 Cov.: 31 AF XY: 0.267 AC XY: 19802 AN XY: 74274

African (AFR) AF: 0.342 AC: 14179 AN: 41422

American (AMR) AF: 0.209 AC: 3189 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 970 AN: 3468

East Asian (EAS) AF: 0.0284 AC: 147 AN: 5172

South Asian (SAS) AF: 0.135 AC: 648 AN: 4802

European-Finnish (FIN) AF: 0.286 AC: 3019 AN: 10544

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.272 AC: 18479 AN: 67986

Other (OTH) AF: 0.262 AC: 553 AN: 2108

Alfa AF: 0.275 Hom.: 796

Bravo AF: 0.271

Asia WGS AF: 0.111 AC: 385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.53
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs729390; hg19: chr9-99012528;