9-96275748-G-A

Variant names:

• chr9-96275748-G-A
• rs2476927
• NM_000197.2:c.202-20805C>T

Variant summary

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

The NM_000197.2(HSD17B3):​c.202-20805C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 151,392 control chromosomes in the GnomAD database, including 12,084 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 0.39 (12084 hom., cov: 30)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 6 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.202-20805C>T		intron_variant	Intron 2 of 10	ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.2969-20805C>T		intron_variant	Intron 17 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.202-20805C>T		intron_variant	Intron 2 of 10	1	NM_000197.2	ENSP00000364412.3
ENSG00000285269	ENST00000643789.1	n.*1878-20805C>T		intron_variant	Intron 13 of 21			ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59390 AN: 151276 Hom.: 12080 Cov.: 30

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.393 AC: 59429 AN: 151392 Hom.: 12084 Cov.: 30 AF XY: 0.388 AC XY: 28697 AN XY: 73928

African (AFR) AF: 0.477 AC: 19678 AN: 41272

American (AMR) AF: 0.270 AC: 4102 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1462 AN: 3462

East Asian (EAS) AF: 0.241 AC: 1242 AN: 5156

South Asian (SAS) AF: 0.266 AC: 1278 AN: 4804

European-Finnish (FIN) AF: 0.400 AC: 4157 AN: 10386

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26293 AN: 67820

Other (OTH) AF: 0.382 AC: 801 AN: 2096

Alfa AF: 0.385 Hom.: 40923

Bravo AF: 0.387

Asia WGS AF: 0.253 AC: 880 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.63
DANN	Benign	0.83
PhyloP100		-1.2
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: rs2476927; hg19: chr9-99038030;