rs8190512

Variant names:

• chr9-96287818-C-A
• rs8190512
• NM_000197.2:c.201+10598G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-96287818-C-A
• chr9-96287818-C-G

Variant summary

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

The NM_000197.2(HSD17B3):​c.201+10598G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 150,488 control chromosomes in the GnomAD database, including 18,344 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 0.48 (18344 hom., cov: 28)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.155
• Publications: 7 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]

HSD17B3 Gene-Disease associations (from GenCC):

• 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000285269 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.201+10598G>T		intron_variant	Intron 2 of 10	ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.2968+10598G>T		intron_variant	Intron 17 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.201+10598G>T		intron_variant	Intron 2 of 10	1	NM_000197.2	ENSP00000364412.3
ENSG00000285269	ENST00000643789.1	n.*1877+10598G>T		intron_variant	Intron 13 of 21			ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 72431 AN: 150380 Hom.: 18330 Cov.: 28

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.403

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.482 AC: 72498 AN: 150488 Hom.: 18344 Cov.: 28 AF XY: 0.483 AC XY: 35522 AN XY: 73520

African (AFR) AF: 0.331 AC: 13576 AN: 40968

American (AMR) AF: 0.558 AC: 8446 AN: 15126

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1648 AN: 3468

East Asian (EAS) AF: 0.658 AC: 3371 AN: 5122

South Asian (SAS) AF: 0.479 AC: 2280 AN: 4758

European-Finnish (FIN) AF: 0.539 AC: 5395 AN: 10016

Middle Eastern (MID) AF: 0.392 AC: 112 AN: 286

European-Non Finnish (NFE) AF: 0.532 AC: 36058 AN: 67744

Other (OTH) AF: 0.488 AC: 1022 AN: 2094

Alfa AF: 0.514 Hom.: 52283

Bravo AF: 0.475

Asia WGS AF: 0.553 AC: 1922 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.0
DANN	Benign	0.81
PhyloP100		-0.15
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: rs8190512; hg19: chr9-99050100;