rs2243595

Variant names:

• chr9-96245625-G-A
• rs2243595
• NM_000197.2:c.525-199C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000197.2(HSD17B3):​c.525-199C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,188 control chromosomes in the GnomAD database, including 56,939 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.86 (56939 hom., cov: 31)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.830
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ENSG00000285269 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 9-96245625-G-A is Benign according to our data. Variant chr9-96245625-G-A is described in ClinVar as Benign. ClinVar VariationId is 1239151.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 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.525-199C>T		intron	N/A	NP_000188.1	P37058-1
	SLC35D2-HSD17B3	NR_182427.1		n.3292-199C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	ENST00000375263.8	TSL:1 MANE Select	c.525-199C>T		intron	N/A	ENSP00000364412.3	P37058-1
	HSD17B3	ENST00000375262.4	TSL:1	c.525-199C>T		intron	N/A	ENSP00000364411.2	P37058-2
	ENSG00000285269	ENST00000643789.1		n.*2201-199C>T		intron	N/A	ENSP00000494818.1	A0A2R8Y5X9

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131388 AN: 152070 Hom.: 56877 Cov.: 31

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.897

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.912

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.851

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

GnomAD4 genome AF: 0.864 AC: 131510 AN: 152188 Hom.: 56939 Cov.: 31 AF XY: 0.866 AC XY: 64385 AN XY: 74380

African (AFR) AF: 0.905 AC: 37574 AN: 41526

American (AMR) AF: 0.849 AC: 12973 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2884 AN: 3472

East Asian (EAS) AF: 0.848 AC: 4377 AN: 5160

South Asian (SAS) AF: 0.769 AC: 3688 AN: 4796

European-Finnish (FIN) AF: 0.912 AC: 9667 AN: 10602

Middle Eastern (MID) AF: 0.813 AC: 239 AN: 294

European-Non Finnish (NFE) AF: 0.845 AC: 57488 AN: 68024

Other (OTH) AF: 0.852 AC: 1802 AN: 2114

Alfa AF: 0.859 Hom.: 9794

Bravo AF: 0.861

Asia WGS AF: 0.813 AC: 2829 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.85
DANN	Benign	0.35
PhyloP100		-0.83
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: rs2243595; hg19: chr9-99007907;