chr9-96255802-C-T

Variant names:

• chr9-96255802-C-T
• rs2479824
• NM_000197.2:c.202-859G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000197.2(HSD17B3):​c.202-859G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 152,122 control chromosomes in the GnomAD database, including 49,052 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 0.80 (49052 hom., cov: 31)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.869
• 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]

ENSG00000285269 (HGNC:):

HSD17B3-AS1 (HGNC:53136): (HSD17B3 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.202-859G>A		intron_variant	Intron 2 of 10	ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.2969-859G>A		intron_variant	Intron 17 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.202-859G>A		intron_variant	Intron 2 of 10	1	NM_000197.2	ENSP00000364412.3
ENSG00000285269	ENST00000643789.1	n.*1878-859G>A		intron_variant	Intron 13 of 21			ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121171 AN: 152004 Hom.: 48986 Cov.: 31

Gnomad AFR AF: 0.945

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.792

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

GnomAD4 genome AF: 0.797 AC: 121296 AN: 152122 Hom.: 49052 Cov.: 31 AF XY: 0.795 AC XY: 59081 AN XY: 74354

African (AFR) AF: 0.945 AC: 39264 AN: 41528

American (AMR) AF: 0.800 AC: 12231 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2607 AN: 3472

East Asian (EAS) AF: 0.717 AC: 3705 AN: 5166

South Asian (SAS) AF: 0.712 AC: 3433 AN: 4820

European-Finnish (FIN) AF: 0.718 AC: 7579 AN: 10560

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.735 AC: 49957 AN: 67976

Other (OTH) AF: 0.793 AC: 1668 AN: 2104

Alfa AF: 0.768 Hom.: 8395

Bravo AF: 0.809

Asia WGS AF: 0.746 AC: 2597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.34
DANN	Benign	0.48
PhyloP100		-0.87
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: rs2479824; hg19: chr9-99018084;