rs8190560

Positions:

• chr9-96239903-C-T

Variant summary

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

The NM_000197.2(HSD17B3):​c.822+855G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0342 in 152,304 control chromosomes in the GnomAD database, including 225 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 0.034 (225 hom., cov: 33)
  • Exomes 𝑓: 0.029 (0 hom.)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.659

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.822+855G>A		intron_variant		ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.3589+855G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.822+855G>A		intron_variant		1	NM_000197.2	ENSP00000364412	P1

Frequencies

GnomAD3 genomes AF: 0.0341 AC: 5193 AN: 152150 Hom.: 222 Cov.: 33

Gnomad AFR AF: 0.00645

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.0800

Gnomad SAS AF: 0.0680

Gnomad FIN AF: 0.0444

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0235

Gnomad OTH AF: 0.0344

GnomAD4 exome AF: 0.0294 AC: 1 AN: 34 Hom.: 0 Cov.: 0 AF XY: 0.0385 AC XY: 1 AN XY: 26

Gnomad4 AMR exome AF: 0.00

Gnomad4 NFE exome AF: 0.0313

GnomAD4 genome AF: 0.0342 AC: 5206 AN: 152270 Hom.: 225 Cov.: 33 AF XY: 0.0380 AC XY: 2832 AN XY: 74438

Gnomad4 AFR AF: 0.00643

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.0277

Gnomad4 EAS AF: 0.0799

Gnomad4 SAS AF: 0.0684

Gnomad4 FIN AF: 0.0444

Gnomad4 NFE AF: 0.0235

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0341 Hom.: 24

Bravo AF: 0.0391

Asia WGS AF: 0.0790 AC: 273 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.12
DANN	Benign	0.30

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: rs8190560; hg19: chr9-99002185;