rs8190566

Positions:

• chr9-96239453-T-C
• chr9-96239453-T-G

Variant summary

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

The NM_000197.2(HSD17B3):​c.822+1305A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,236 control chromosomes in the GnomAD database, including 2,014 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 0.13 (2014 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840

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 (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B3	NM_000197.2	c.822+1305A>G		intron_variant		ENST00000375263.8
SLC35D2-HSD17B3	NR_182427.1	n.3589+1305A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B3	ENST00000375263.8	c.822+1305A>G		intron_variant		1	NM_000197.2	P1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20138 AN: 152118 Hom.: 2002 Cov.: 33

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0814

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0819

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0637

Gnomad OTH AF: 0.127

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.133 AC: 20179 AN: 152236 Hom.: 2014 Cov.: 33 AF XY: 0.134 AC XY: 9960 AN XY: 74438

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.0811

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0819

Gnomad4 NFE AF: 0.0637

Gnomad4 OTH AF: 0.125

Alfa AF: 0.0940 Hom.: 152

Bravo AF: 0.140

Asia WGS AF: 0.173 AC: 604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.5
DANN	Benign	0.45

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: rs8190566; hg19: chr9-99001735;