rs2253502

Variant names:

• chr9-96246161-G-A
• rs2253502
• NM_000197.2:c.524+395C>T

Your query was ambiguous. Multiple possible variants found:

• chr9-96246161-G-A
• chr9-96246161-G-C
• chr9-96246161-G-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.524+395C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 152,150 control chromosomes in the GnomAD database, including 45,490 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 0.77 (45490 hom., cov: 33)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.667
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.524+395C>T		intron_variant	Intron 7 of 10	ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.3291+395C>T		intron_variant	Intron 22 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.524+395C>T		intron_variant	Intron 7 of 10	1	NM_000197.2	ENSP00000364412.3
ENSG00000285269	ENST00000643789.1	n.*2200+395C>T		intron_variant	Intron 18 of 21			ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117357 AN: 152032 Hom.: 45450 Cov.: 33

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.781

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.772 AC: 117456 AN: 152150 Hom.: 45490 Cov.: 33 AF XY: 0.770 AC XY: 57290 AN XY: 74390

African (AFR) AF: 0.778 AC: 32287 AN: 41508

American (AMR) AF: 0.781 AC: 11947 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2430 AN: 3472

East Asian (EAS) AF: 0.609 AC: 3143 AN: 5162

South Asian (SAS) AF: 0.658 AC: 3169 AN: 4816

European-Finnish (FIN) AF: 0.829 AC: 8769 AN: 10584

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.782 AC: 53176 AN: 68000

Other (OTH) AF: 0.754 AC: 1590 AN: 2108

Alfa AF: 0.774 Hom.: 13533

Bravo AF: 0.768

Asia WGS AF: 0.648 AC: 2250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.35
DANN	Benign	0.17
PhyloP100		-0.67
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: rs2253502; hg19: chr9-99008443;