chr9-96301920-C-CA

Variant names:

• chr9-96301920-C-CA
• rs8190483
• NM_000197.2:c.154+30dupT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000197.2(HSD17B3):​c.154+30dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,602,790 control chromosomes in the GnomAD database, including 120,084 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (8036 hom., cov: 19)
  • Exomes 𝑓: 0.38 (112048 hom.)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.71
• 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]

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 -16 ACMG points.

• BP6: Variant 9-96301920-C-CA is Benign according to our data. Variant chr9-96301920-C-CA is described in ClinVar as Benign. ClinVar VariationId is 255508.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.421 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.154+30dupT		intron	N/A	NP_000188.1
	SLC35D2-HSD17B3	NR_182427.1		n.2921+30dupT		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	ENST00000375263.8	TSL:1 MANE Select	c.154+30_154+31insT		intron	N/A	ENSP00000364412.3
	HSD17B3	ENST00000375262.4	TSL:1	c.154+30_154+31insT		intron	N/A	ENSP00000364411.2
	ENSG00000285269	ENST00000643789.1		n.*1830+30_*1830+31insT		intron	N/A	ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43471 AN: 151546 Hom.: 8039 Cov.: 19

Gnomad AFR AF: 0.0849

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.336

Gnomad EAS AF: 0.0646

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.295

GnomAD2 exomes AF: 0.306 AC: 76738 AN: 250938 AF XY: 0.311

Gnomad AFR exome AF: 0.0765

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.334

Gnomad EAS exome AF: 0.0560

Gnomad FIN exome AF: 0.374

Gnomad NFE exome AF: 0.422

Gnomad OTH exome AF: 0.338

GnomAD4 exome AF: 0.379 AC: 550348 AN: 1451126 Hom.: 112048 Cov.: 31 AF XY: 0.375 AC XY: 271191 AN XY: 722608

African (AFR) AF: 0.0706 AC: 2359 AN: 33416

American (AMR) AF: 0.216 AC: 9665 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 8715 AN: 26056

East Asian (EAS) AF: 0.0698 AC: 2769 AN: 39656

South Asian (SAS) AF: 0.188 AC: 16149 AN: 86126

European-Finnish (FIN) AF: 0.379 AC: 20213 AN: 53300

Middle Eastern (MID) AF: 0.256 AC: 1469 AN: 5746

European-Non Finnish (NFE) AF: 0.425 AC: 468728 AN: 1102076

Other (OTH) AF: 0.338 AC: 20281 AN: 60040

GnomAD4 genome AF: 0.287 AC: 43460 AN: 151664 Hom.: 8036 Cov.: 19 AF XY: 0.278 AC XY: 20600 AN XY: 74034

African (AFR) AF: 0.0846 AC: 3505 AN: 41408

American (AMR) AF: 0.247 AC: 3757 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 1165 AN: 3464

East Asian (EAS) AF: 0.0645 AC: 332 AN: 5144

South Asian (SAS) AF: 0.173 AC: 832 AN: 4800

European-Finnish (FIN) AF: 0.366 AC: 3830 AN: 10454

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.425 AC: 28869 AN: 67894

Other (OTH) AF: 0.291 AC: 611 AN: 2098

Alfa AF: 0.317 Hom.: 1826

Bravo AF: 0.266

Asia WGS AF: 0.109 AC: 379 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.7
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: rs8190483; hg19: chr9-99064202; COSMIC: COSV100931318;