rs8190534

chr9-96255999-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000197.2(HSD17B3):c.202-1056G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,172 control chromosomes in the GnomAD database, including 3,335 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 0.20 (3335 hom., cov: 32)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B3	NM_000197.2	c.202-1056G>C		intron_variant		ENST00000375263.8
SLC35D2-HSD17B3	NR_182427.1	n.2969-1056G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B3	ENST00000375263.8	c.202-1056G>C		intron_variant		1	NM_000197.2	P1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30921 AN: 152054 Hom.: 3334 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.203 AC: 30942 AN: 152172 Hom.: 3335 Cov.: 32 AF XY: 0.211 AC XY: 15675 AN XY: 74406

Gnomad4 AFR AF: 0.170

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.193

Alfa AF: 0.203 Hom.: 400

Bravo AF: 0.197

Asia WGS AF: 0.331 AC: 1150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.5
Dann	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs8190534; hg19: chr9-99018281;