rs8190531

Positions:

• chr9-96265532-A-G

Variant summary

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

The NM_000197.2(HSD17B3):​c.202-10589T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,088 control chromosomes in the GnomAD database, including 17,939 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 (17939 hom., cov: 33)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.202-10589T>C		intron_variant		ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.2969-10589T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.202-10589T>C		intron_variant		1	NM_000197.2	ENSP00000364412	P1

Frequencies

GnomAD3 genomes AF: 0.476 AC: 72407 AN: 151970 Hom.: 17938 Cov.: 33

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.476 AC: 72450 AN: 152088 Hom.: 17939 Cov.: 33 AF XY: 0.474 AC XY: 35260 AN XY: 74340

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.485

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.487

Alfa AF: 0.520 Hom.: 5204

Bravo AF: 0.466

Asia WGS AF: 0.497 AC: 1725 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.4
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs8190531; hg19: chr9-99027814;