rs8190540

Positions:

• chr9-96252111-C-CAACT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000197.2(HSD17B3):​c.386-627_386-626insAGTT 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

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]

SLC35D2-HSD17B3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.386-627_386-626insAGTT		intron_variant		ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.3153-627_3153-626insAGTT		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.386-627_386-626insAGTT		intron_variant		1	NM_000197.2	ENSP00000364412	P1

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

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.0281

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.246

Alfa AF: 0.259 Hom.: 644

Asia WGS AF: 0.107 AC: 371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8190540; hg19: chr9-99014393;