rs8190495

Variant names:

• chr9-96299602-A-G
• rs8190495
• NM_000197.2:c.155-1140T>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.155-1140T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,098 control chromosomes in the GnomAD database, including 7,577 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 0.30 (7577 hom., cov: 31)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 2 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.155-1140T>C		intron_variant	Intron 1 of 10	ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.2922-1140T>C		intron_variant	Intron 16 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.155-1140T>C		intron_variant	Intron 1 of 10	1	NM_000197.2	ENSP00000364412.3
ENSG00000285269	ENST00000643789.1	n.*1831-1140T>C		intron_variant	Intron 12 of 21			ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45746 AN: 151980 Hom.: 7574 Cov.: 31

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.0620

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.301 AC: 45763 AN: 152098 Hom.: 7577 Cov.: 31 AF XY: 0.294 AC XY: 21827 AN XY: 74334

African (AFR) AF: 0.218 AC: 9034 AN: 41476

American (AMR) AF: 0.245 AC: 3737 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1084 AN: 3470

East Asian (EAS) AF: 0.0620 AC: 321 AN: 5180

South Asian (SAS) AF: 0.126 AC: 608 AN: 4826

European-Finnish (FIN) AF: 0.367 AC: 3876 AN: 10568

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25926 AN: 67988

Other (OTH) AF: 0.291 AC: 615 AN: 2114

Alfa AF: 0.329 Hom.: 1340

Bravo AF: 0.289

Asia WGS AF: 0.102 AC: 357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.0
DANN	Benign	0.71
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs8190495; hg19: chr9-99061884;