9-96293927-A-G

Variant names:

• chr9-96293927-A-G
• rs11788083
• NM_000197.2:c.201+4489T>C

Variant summary

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

The ENST00000375263.8(HSD17B3):​c.201+4489T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,066 control chromosomes in the GnomAD database, including 2,459 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 0.17 (2459 hom., cov: 32)
• Consequence: HSD17B3 ENST00000375263.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000375263.8. 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.201+4489T>C		intron	N/A	NP_000188.1
	SLC35D2-HSD17B3	NR_182427.1		n.2968+4489T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	ENST00000375263.8	TSL:1 MANE Select	c.201+4489T>C		intron	N/A	ENSP00000364412.3
	HSD17B3	ENST00000375262.4	TSL:1	c.201+4489T>C		intron	N/A	ENSP00000364411.2
	ENSG00000285269	ENST00000643789.1		n.*1877+4489T>C		intron	N/A	ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25327 AN: 151948 Hom.: 2456 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0725

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.167 AC: 25357 AN: 152066 Hom.: 2459 Cov.: 32 AF XY: 0.173 AC XY: 12879 AN XY: 74292

African (AFR) AF: 0.140 AC: 5792 AN: 41494

American (AMR) AF: 0.299 AC: 4560 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 513 AN: 3468

East Asian (EAS) AF: 0.295 AC: 1518 AN: 5154

South Asian (SAS) AF: 0.255 AC: 1226 AN: 4812

European-Finnish (FIN) AF: 0.167 AC: 1764 AN: 10572

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9508 AN: 67998

Other (OTH) AF: 0.172 AC: 364 AN: 2112

Alfa AF: 0.150 Hom.: 7681

Bravo AF: 0.175

Asia WGS AF: 0.249 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.84
PhyloP100		-0.21
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: rs11788083; hg19: chr9-99056209;