rs8190540

Variant names:

• chr9-96252111-C-CAACT
• rs8190540
• NM_000197.2:c.386-630_386-627dupAGTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000197.2(HSD17B3):​c.386-630_386-627dupAGTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 151,984 control chromosomes in the GnomAD database, including 5,301 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5301 hom., cov: 21)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.639
• 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]

ENSG00000285269 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000197.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	NM_000197.2	MANE Select	c.386-630_386-627dupAGTT		intron	N/A	NP_000188.1	P37058-1
	SLC35D2-HSD17B3	NR_182427.1		n.3153-630_3153-627dupAGTT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	ENST00000375263.8	TSL:1 MANE Select	c.386-630_386-627dupAGTT		intron	N/A	ENSP00000364412.3	P37058-1
	HSD17B3	ENST00000375262.4	TSL:1	c.386-630_386-627dupAGTT		intron	N/A	ENSP00000364411.2	P37058-2
	ENSG00000285269	ENST00000643789.1		n.*2062-630_*2062-627dupAGTT		intron	N/A	ENSP00000494818.1	A0A2R8Y5X9

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39236 AN: 151866 Hom.: 5294 Cov.: 21

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.0281

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.258 AC: 39277 AN: 151984 Hom.: 5301 Cov.: 21 AF XY: 0.252 AC XY: 18722 AN XY: 74310

African (AFR) AF: 0.305 AC: 12625 AN: 41412

American (AMR) AF: 0.197 AC: 3006 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 940 AN: 3468

East Asian (EAS) AF: 0.0281 AC: 146 AN: 5192

South Asian (SAS) AF: 0.135 AC: 653 AN: 4822

European-Finnish (FIN) AF: 0.270 AC: 2850 AN: 10546

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.267 AC: 18171 AN: 67942

Other (OTH) AF: 0.246 AC: 519 AN: 2112

Alfa AF: 0.259 Hom.: 644

Asia WGS AF: 0.107 AC: 371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8190540; hg19: chr9-99014393;