NM_000197.2:c.202-12732G>A

Variant names:

• chr9-96267675-C-T
• rs8190530
• NM_000197.2:c.202-12732G>A

Variant summary

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

The NM_000197.2(HSD17B3):​c.202-12732G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 151,260 control chromosomes in the GnomAD database, including 6,818 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 0.28 (6818 hom., cov: 31)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.911
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.202-12732G>A		intron_variant	Intron 2 of 10	ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.2969-12732G>A		intron_variant	Intron 17 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.202-12732G>A		intron_variant	Intron 2 of 10	1	NM_000197.2	ENSP00000364412.3
ENSG00000285269	ENST00000643789.1	n.*1878-12732G>A		intron_variant	Intron 13 of 21			ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42738 AN: 151142 Hom.: 6821 Cov.: 31

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.0589

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.283 AC: 42741 AN: 151260 Hom.: 6818 Cov.: 31 AF XY: 0.275 AC XY: 20293 AN XY: 73844

African (AFR) AF: 0.174 AC: 7147 AN: 41138

American (AMR) AF: 0.247 AC: 3752 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1113 AN: 3462

East Asian (EAS) AF: 0.0588 AC: 302 AN: 5134

South Asian (SAS) AF: 0.127 AC: 605 AN: 4756

European-Finnish (FIN) AF: 0.330 AC: 3441 AN: 10424

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

European-Non Finnish (NFE) AF: 0.372 AC: 25245 AN: 67834

Other (OTH) AF: 0.270 AC: 569 AN: 2104

Alfa AF: 0.323 Hom.: 1928

Bravo AF: 0.271

Asia WGS AF: 0.103 AC: 359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.63
PhyloP100		0.91
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8190530; hg19: chr9-99029957;