chr9-96249995-C-T

Position:

• chr9-96249995-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000375263.8(HSD17B3):​c.454-209G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,459,970 control chromosomes in the GnomAD database, including 52,993 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6628 hom., cov: 32)
  • Exomes 𝑓: 0.26 (46365 hom.)
• Consequence: HSD17B3 ENST00000375263.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.901

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-AS1 (HGNC:53136): (HSD17B3 antisense RNA 1)

SLC35D2-HSD17B3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 9-96249995-C-T is Benign according to our data. Variant chr9-96249995-C-T is described in ClinVar as [Benign]. Clinvar id is 1182347.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.454-209G>A		intron_variant		ENST00000375263.8	NP_000188.1
HSD17B3-AS1	NR_146524.1	n.673C>T		non_coding_transcript_exon_variant	3/3
SLC35D2-HSD17B3	NR_182427.1	n.3221-209G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.454-209G>A		intron_variant		1	NM_000197.2	ENSP00000364412	P1
HSD17B3-AS1	ENST00000448857.1	n.674C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43112 AN: 151952 Hom.: 6619 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.0283

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.259 AC: 338578 AN: 1307900 Hom.: 46365 Cov.: 31 AF XY: 0.255 AC XY: 162774 AN XY: 637162

Gnomad4 AFR exome AF: 0.396

Gnomad4 AMR exome AF: 0.163

Gnomad4 ASJ exome AF: 0.275

Gnomad4 EAS exome AF: 0.0211

Gnomad4 SAS exome AF: 0.145

Gnomad4 FIN exome AF: 0.279

Gnomad4 NFE exome AF: 0.272

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.284 AC: 43156 AN: 152070 Hom.: 6628 Cov.: 32 AF XY: 0.277 AC XY: 20569 AN XY: 74336

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.0284

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.272

Alfa AF: 0.266 Hom.: 7559

Bravo AF: 0.283

Asia WGS AF: 0.113 AC: 393 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	-0.93
CADD	Benign	0.31
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs407179; hg19: chr9-99012277;