9-96251334-C-T

Position:

• chr9-96251334-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

SLC35D2-HSD17B3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.453+84G>A		intron_variant		ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.3220+84G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.453+84G>A		intron_variant		1	NM_000197.2	ENSP00000364412	P1

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

Gnomad4 AFR exome AF: 0.370

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.310

Gnomad4 EAS exome AF: 0.0219

Gnomad4 SAS exome AF: 0.185

Gnomad4 FIN exome AF: 0.292

Gnomad4 NFE exome AF: 0.293

Gnomad4 OTH exome AF: 0.271

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

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.0292

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.281

Alfa AF: 0.202 Hom.: 644

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs8190541; hg19: chr9-99013616;