chr9-96247875-C-T

Variant names:

• chr9-96247875-C-T
• rs912461
• NM_000197.2:c.490-1285G>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.490-1285G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 152,008 control chromosomes in the GnomAD database, including 26,344 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 0.59 (26344 hom., cov: 32)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.867
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	NM_000197.2	MANE Select	c.490-1285G>A		intron	N/A	NP_000188.1
	HSD17B3-AS1	NR_146524.1		n.260+540C>T		intron	N/A
	SLC35D2-HSD17B3	NR_182427.1		n.3257-1285G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	ENST00000375263.8	TSL:1 MANE Select	c.490-1285G>A		intron	N/A	ENSP00000364412.3
	HSD17B3	ENST00000375262.4	TSL:1	c.490-1285G>A		intron	N/A	ENSP00000364411.2
	ENSG00000285269	ENST00000643789.1		n.*2166-1285G>A		intron	N/A	ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.586 AC: 89006 AN: 151890 Hom.: 26314 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.586

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

GnomAD4 genome AF: 0.586 AC: 89081 AN: 152008 Hom.: 26344 Cov.: 32 AF XY: 0.594 AC XY: 44147 AN XY: 74306

African (AFR) AF: 0.546 AC: 22636 AN: 41432

American (AMR) AF: 0.644 AC: 9838 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1924 AN: 3470

East Asian (EAS) AF: 0.820 AC: 4241 AN: 5174

South Asian (SAS) AF: 0.629 AC: 3025 AN: 4808

European-Finnish (FIN) AF: 0.624 AC: 6591 AN: 10560

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.572 AC: 38887 AN: 67980

Other (OTH) AF: 0.587 AC: 1239 AN: 2110

Alfa AF: 0.589 Hom.: 3428

Bravo AF: 0.585

Asia WGS AF: 0.700 AC: 2435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.61
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: rs912461; hg19: chr9-99010157;