9-96251195-G-A

Position:

• chr9-96251195-G-A

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+223C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0281 in 591,618 control chromosomes in the GnomAD database, including 403 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (62 hom., cov: 32)
  • Exomes 𝑓: 0.031 (341 hom.)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.157

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=-0.67).
• BP6: Variant 9-96251195-G-A is Benign according to our data. Variant chr9-96251195-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1194375.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.453+223C>T		intron_variant		ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.3220+223C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.453+223C>T		intron_variant		1	NM_000197.2	ENSP00000364412	P1

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3160 AN: 152192 Hom.: 60 Cov.: 32

Gnomad AFR AF: 0.00386

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.00779

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.0713

Gnomad SAS AF: 0.0642

Gnomad FIN AF: 0.0437

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0230

Gnomad OTH AF: 0.0168

GnomAD4 exome AF: 0.0306 AC: 13436 AN: 439308 Hom.: 341 Cov.: 0 AF XY: 0.0316 AC XY: 7297 AN XY: 230850

Gnomad4 AFR exome AF: 0.00365

Gnomad4 AMR exome AF: 0.0101

Gnomad4 ASJ exome AF: 0.0211

Gnomad4 EAS exome AF: 0.0989

Gnomad4 SAS exome AF: 0.0515

Gnomad4 FIN exome AF: 0.0387

Gnomad4 NFE exome AF: 0.0223

Gnomad4 OTH exome AF: 0.0237

GnomAD4 genome AF: 0.0208 AC: 3171 AN: 152310 Hom.: 62 Cov.: 32 AF XY: 0.0225 AC XY: 1674 AN XY: 74478

Gnomad4 AFR AF: 0.00385

Gnomad4 AMR AF: 0.00778

Gnomad4 ASJ AF: 0.0213

Gnomad4 EAS AF: 0.0715

Gnomad4 SAS AF: 0.0647

Gnomad4 FIN AF: 0.0437

Gnomad4 NFE AF: 0.0230

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0271 Hom.: 10

Bravo AF: 0.0161

Asia WGS AF: 0.0610 AC: 210 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 20, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Benign	0.80

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: rs8190542; hg19: chr9-99013477;