chr9-96288512-A-G

Variant names:

• chr9-96288512-A-G
• rs2479828
• NM_000197.2:c.201+9904T>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.201+9904T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.914 in 152,138 control chromosomes in the GnomAD database, including 63,720 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 0.91 (63720 hom., cov: 31)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.177
• 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]

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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ENSG00000285269 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.95 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.201+9904T>C		intron	N/A	NP_000188.1	P37058-1
	SLC35D2-HSD17B3	NR_182427.1		n.2968+9904T>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.201+9904T>C		intron	N/A	ENSP00000364412.3	P37058-1
	HSD17B3	ENST00000375262.4	TSL:1	c.201+9904T>C		intron	N/A	ENSP00000364411.2	P37058-2
	ENSG00000285269	ENST00000643789.1		n.*1877+9904T>C		intron	N/A	ENSP00000494818.1	A0A2R8Y5X9

Frequencies

GnomAD3 genomes AF: 0.914 AC: 138973 AN: 152020 Hom.: 63660 Cov.: 31

Gnomad AFR AF: 0.957

Gnomad AMI AF: 0.970

Gnomad AMR AF: 0.875

Gnomad ASJ AF: 0.888

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.895

Gnomad MID AF: 0.883

Gnomad NFE AF: 0.910

Gnomad OTH AF: 0.909

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

GnomAD4 genome AF: 0.914 AC: 139095 AN: 152138 Hom.: 63720 Cov.: 31 AF XY: 0.909 AC XY: 67636 AN XY: 74372

African (AFR) AF: 0.957 AC: 39743 AN: 41508

American (AMR) AF: 0.875 AC: 13364 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.888 AC: 3083 AN: 3472

East Asian (EAS) AF: 0.923 AC: 4766 AN: 5162

South Asian (SAS) AF: 0.768 AC: 3696 AN: 4810

European-Finnish (FIN) AF: 0.895 AC: 9466 AN: 10572

Middle Eastern (MID) AF: 0.874 AC: 257 AN: 294

European-Non Finnish (NFE) AF: 0.910 AC: 61916 AN: 68018

Other (OTH) AF: 0.909 AC: 1919 AN: 2110

Alfa AF: 0.906 Hom.: 124141

Bravo AF: 0.916

Asia WGS AF: 0.830 AC: 2889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.9
DANN	Benign	0.69
PhyloP100		-0.18
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: rs2479828; hg19: chr9-99050794;