rs8190534

Variant names:

• chr9-96255999-C-G
• rs8190534
• NM_000197.2:c.202-1056G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000197.2(HSD17B3):​c.202-1056G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,172 control chromosomes in the GnomAD database, including 3,335 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 0.20 (3335 hom., cov: 32)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• Publications: 5 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)

RNU6-1160P (HGNC:48123): (RNA, U6 small nuclear 1160, pseudogene)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	NM_000197.2	MANE Select	c.202-1056G>C		intron	N/A	NP_000188.1	P37058-1
	SLC35D2-HSD17B3	NR_182427.1		n.2969-1056G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	ENST00000375263.8	TSL:1 MANE Select	c.202-1056G>C		intron	N/A	ENSP00000364412.3	P37058-1
	HSD17B3	ENST00000375262.4	TSL:1	c.202-1056G>C		intron	N/A	ENSP00000364411.2	P37058-2
	ENSG00000285269	ENST00000643789.1		n.*1878-1056G>C		intron	N/A	ENSP00000494818.1	A0A2R8Y5X9

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30921 AN: 152054 Hom.: 3334 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.315

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.203 AC: 30942 AN: 152172 Hom.: 3335 Cov.: 32 AF XY: 0.211 AC XY: 15675 AN XY: 74406

African (AFR) AF: 0.170 AC: 7060 AN: 41522

American (AMR) AF: 0.234 AC: 3574 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 539 AN: 3470

East Asian (EAS) AF: 0.314 AC: 1625 AN: 5170

South Asian (SAS) AF: 0.349 AC: 1682 AN: 4822

European-Finnish (FIN) AF: 0.235 AC: 2489 AN: 10598

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.197 AC: 13366 AN: 67990

Other (OTH) AF: 0.193 AC: 406 AN: 2108

Alfa AF: 0.203 Hom.: 400

Bravo AF: 0.197

Asia WGS AF: 0.331 AC: 1150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.5
DANN	Benign	0.47
PhyloP100		0.096
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8190534; hg19: chr9-99018281;