rs2243595

Positions:

• chr9-96245625-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000285269 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.525-199C>T		intron_variant		ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.3292-199C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.525-199C>T		intron_variant		1	NM_000197.2	ENSP00000364412.3
ENSG00000285269	ENST00000643789.1	n.*2201-199C>T		intron_variant				ENSP00000494818.1

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

Gnomad4 AFR AF: 0.905

Gnomad4 AMR AF: 0.849

Gnomad4 ASJ AF: 0.831

Gnomad4 EAS AF: 0.848

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.912

Gnomad4 NFE AF: 0.845

Gnomad4 OTH AF: 0.852

Alfa AF: 0.858 Hom.: 9469

Bravo AF: 0.861

Asia WGS AF: 0.813 AC: 2829 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.85
DANN	Benign	0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs2243595; hg19: chr9-99007907;