rs1927883

Positions:

• chr9-96240312-G-A

Variant summary

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

The NM_000197.2(HSD17B3):​c.822+446C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 152,084 control chromosomes in the GnomAD database, including 28,915 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 0.61 (28915 hom., cov: 33)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.791

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.822+446C>T		intron_variant		ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.3589+446C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.822+446C>T		intron_variant		1	NM_000197.2	ENSP00000364412	P1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93397 AN: 151964 Hom.: 28883 Cov.: 33

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.615 AC: 93480 AN: 152084 Hom.: 28915 Cov.: 33 AF XY: 0.621 AC XY: 46182 AN XY: 74348

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.819

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.604

Alfa AF: 0.597 Hom.: 5605

Bravo AF: 0.618

Asia WGS AF: 0.710 AC: 2468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.5
DANN	Benign	0.34

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: rs1927883; hg19: chr9-99002594;