9-96251334-C-T

Variant names:

• chr9-96251334-C-T
• rs8190541
• NM_000197.2:c.453+84G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000197.2(HSD17B3):​c.453+84G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,164,074 control chromosomes in the GnomAD database, including 46,355 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6927 hom., cov: 31)
  • Exomes 𝑓: 0.27 (39428 hom.)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0140
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-96251334-C-T is Benign according to our data. Variant chr9-96251334-C-T is described in ClinVar as Benign. ClinVar VariationId is 1237994.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 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.453+84G>A		intron	N/A	NP_000188.1
	SLC35D2-HSD17B3	NR_182427.1		n.3220+84G>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.453+84G>A		intron	N/A	ENSP00000364412.3
	HSD17B3	ENST00000375262.4	TSL:1	c.453+84G>A		intron	N/A	ENSP00000364411.2
	ENSG00000285269	ENST00000643789.1		n.*2129+84G>A		intron	N/A	ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44339 AN: 151866 Hom.: 6919 Cov.: 31

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.0291

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.270 AC: 273023 AN: 1012090 Hom.: 39428 Cov.: 14 AF XY: 0.267 AC XY: 139023 AN XY: 521550

African (AFR) AF: 0.370 AC: 9200 AN: 24864

American (AMR) AF: 0.141 AC: 6064 AN: 43046

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 7191 AN: 23190

East Asian (EAS) AF: 0.0219 AC: 820 AN: 37472

South Asian (SAS) AF: 0.185 AC: 14120 AN: 76436

European-Finnish (FIN) AF: 0.292 AC: 15227 AN: 52080

Middle Eastern (MID) AF: 0.390 AC: 1885 AN: 4838

European-Non Finnish (NFE) AF: 0.293 AC: 206167 AN: 704586

Other (OTH) AF: 0.271 AC: 12349 AN: 45578

GnomAD4 genome AF: 0.292 AC: 44384 AN: 151984 Hom.: 6927 Cov.: 31 AF XY: 0.286 AC XY: 21240 AN XY: 74290

African (AFR) AF: 0.362 AC: 15001 AN: 41426

American (AMR) AF: 0.217 AC: 3315 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1045 AN: 3466

East Asian (EAS) AF: 0.0292 AC: 151 AN: 5178

South Asian (SAS) AF: 0.170 AC: 820 AN: 4816

European-Finnish (FIN) AF: 0.296 AC: 3129 AN: 10554

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.293 AC: 19949 AN: 67970

Other (OTH) AF: 0.281 AC: 592 AN: 2108

Alfa AF: 0.208 Hom.: 693

Bravo AF: 0.288

Asia WGS AF: 0.126 AC: 437 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Aug 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.62
PhyloP100		0.014
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs8190541; hg19: chr9-99013616;