chr9-96235779-T-G

Variant names:

• chr9-96235779-T-G
• rs8190569
• NM_000197.2:c.823-209A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000197.2(HSD17B3):​c.823-209A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 152,304 control chromosomes in the GnomAD database, including 30 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 0.015 (30 hom., cov: 31)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277
• 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=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0154 (2351/152304) while in subpopulation NFE AF = 0.0254 (1725/68034). AF 95% confidence interval is 0.0244. There are 30 homozygotes in GnomAd4. There are 1105 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 30 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	NM_000197.2	MANE Select	c.823-209A>C		intron	N/A	NP_000188.1
	SLC35D2-HSD17B3	NR_182427.1		n.3590-209A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	ENST00000375263.8	TSL:1 MANE Select	c.823-209A>C		intron	N/A	ENSP00000364412.3
	HSD17B3	ENST00000375262.4	TSL:1	c.673-209A>C		intron	N/A	ENSP00000364411.2
	ENSG00000285269	ENST00000643789.1		n.*2499-209A>C		intron	N/A	ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2349 AN: 152186 Hom.: 30 Cov.: 31

Gnomad AFR AF: 0.00425

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0254

Gnomad OTH AF: 0.0105

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

GnomAD4 genome AF: 0.0154 AC: 2351 AN: 152304 Hom.: 30 Cov.: 31 AF XY: 0.0148 AC XY: 1105 AN XY: 74464

African (AFR) AF: 0.00421 AC: 175 AN: 41568

American (AMR) AF: 0.0126 AC: 192 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 59 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5168

South Asian (SAS) AF: 0.00539 AC: 26 AN: 4828

European-Finnish (FIN) AF: 0.0137 AC: 145 AN: 10622

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0254 AC: 1725 AN: 68034

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.0201 Hom.: 5

Bravo AF: 0.0148

Asia WGS AF: 0.00173 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.64
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism

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: rs8190569; hg19: chr9-98998061;