rs8190541

Variant names:

• chr9-96251334-C-A
• rs8190541
• NM_000197.2:c.453+84G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-96251334-C-A
• chr9-96251334-C-G
• chr9-96251334-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000197.2(HSD17B3):​c.453+84G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000296 in 1,014,276 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140
• Publications: 0 publications found

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]

ENSG00000285269 (HGNC:):

HSD17B3-AS1 (HGNC:53136): (HSD17B3 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000197.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	NM_000197.2	MANE Select	c.453+84G>T		intron	N/A	NP_000188.1
	SLC35D2-HSD17B3	NR_182427.1		n.3220+84G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	ENST00000375263.8	TSL:1 MANE Select	c.453+84G>T		intron	N/A	ENSP00000364412.3
	HSD17B3	ENST00000375262.4	TSL:1	c.453+84G>T		intron	N/A	ENSP00000364411.2
	ENSG00000285269	ENST00000643789.1		n.*2129+84G>T		intron	N/A	ENSP00000494818.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000296 AC: 3 AN: 1014276 Hom.: 0 Cov.: 14 AF XY: 0.00000574 AC XY: 3 AN XY: 522586

African (AFR) AF: 0.00 AC: 0 AN: 24922

American (AMR) AF: 0.00 AC: 0 AN: 43082

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23214

East Asian (EAS) AF: 0.0000267 AC: 1 AN: 37474

South Asian (SAS) AF: 0.00 AC: 0 AN: 76494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4844

European-Non Finnish (NFE) AF: 0.00000142 AC: 1 AN: 706450

Other (OTH) AF: 0.0000219 AC: 1 AN: 45662

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.65
PhyloP100		0.014

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8190541; hg19: chr9-99013616;