rs12552648

chr9-96239213-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+1545G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 152,456 control chromosomes in the GnomAD database, including 439 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 0.063 (439 hom., cov: 32)
  • Exomes 𝑓: 0.031 (0 hom.)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B3	NM_000197.2	c.822+1545G>A		intron_variant		ENST00000375263.8
SLC35D2-HSD17B3	NR_182427.1	n.3589+1545G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B3	ENST00000375263.8	c.822+1545G>A		intron_variant		1	NM_000197.2	P1

Frequencies

GnomAD3 genomes AF: 0.0629 AC: 9565 AN: 152112 Hom.: 441 Cov.: 32

Gnomad AFR AF: 0.0618

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0533

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.0766

Gnomad FIN AF: 0.0465

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0497

Gnomad OTH AF: 0.0803

GnomAD4 exome AF: 0.0310 AC: 7 AN: 226 Hom.: 0 AF XY: 0.0325 AC XY: 5 AN XY: 154

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0405

Gnomad4 NFE exome AF: 0.0246

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0628 AC: 9563 AN: 152230 Hom.: 439 Cov.: 32 AF XY: 0.0637 AC XY: 4739 AN XY: 74434

Gnomad4 AFR AF: 0.0619

Gnomad4 AMR AF: 0.0530

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.0764

Gnomad4 FIN AF: 0.0465

Gnomad4 NFE AF: 0.0497

Gnomad4 OTH AF: 0.0790

Alfa AF: 0.0487 Hom.: 29

Bravo AF: 0.0653

Asia WGS AF: 0.144 AC: 503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.23
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: rs12552648; hg19: chr9-99001495;