rs8190512

chr9-96287818-C-Achr9-96287818-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.201+10598G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 150,488 control chromosomes in the GnomAD database, including 18,344 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 0.48 (18344 hom., cov: 28)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B3	NM_000197.2	c.201+10598G>T		intron_variant		ENST00000375263.8
SLC35D2-HSD17B3	NR_182427.1	n.2968+10598G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B3	ENST00000375263.8	c.201+10598G>T		intron_variant		1	NM_000197.2	P1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 72431 AN: 150380 Hom.: 18330 Cov.: 28

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.403

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.482 AC: 72498 AN: 150488 Hom.: 18344 Cov.: 28 AF XY: 0.483 AC XY: 35522 AN XY: 73520

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.558

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.532

Gnomad4 OTH AF: 0.488

Alfa AF: 0.518 Hom.: 38032

Bravo AF: 0.475

Asia WGS AF: 0.553 AC: 1922 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	6.0
Dann	Benign	0.81

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: rs8190512; hg19: chr9-99050100;