9-96235628-ATCTTTGTGG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000197.2(HSD17B3):c.823-67_823-59del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,336,852 control chromosomes in the GnomAD database, including 149,529 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (14699 hom., cov: 0)
  • Exomes 𝑓: 0.47 (134830 hom.)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.491

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 -10 ACMG points.

• BP6: Variant 9-96235628-ATCTTTGTGG-A is Benign according to our data. Variant chr9-96235628-ATCTTTGTGG-A is described in ClinVar as [Benign]. Clinvar id is 1220642.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-96235628-ATCTTTGTGG-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B3	NM_000197.2	c.823-67_823-59del		intron_variant		ENST00000375263.8
SLC35D2-HSD17B3	NR_182427.1	n.3590-67_3590-59del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B3	ENST00000375263.8	c.823-67_823-59del		intron_variant		1	NM_000197.2	P1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65751 AN: 151486 Hom.: 14687 Cov.: 0

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.340

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.429

GnomAD4 exome AF: 0.473 AC: 560677 AN: 1185246 Hom.: 134830 AF XY: 0.474 AC XY: 283934 AN XY: 598496

Gnomad4 AFR exome AF: 0.309

Gnomad4 AMR exome AF: 0.413

Gnomad4 ASJ exome AF: 0.385

Gnomad4 EAS exome AF: 0.473

Gnomad4 SAS exome AF: 0.453

Gnomad4 FIN exome AF: 0.507

Gnomad4 NFE exome AF: 0.485

Gnomad4 OTH exome AF: 0.460

GnomAD4 genome AF: 0.434 AC: 65784 AN: 151606 Hom.: 14699 Cov.: 0 AF XY: 0.435 AC XY: 32248 AN XY: 74078

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.482

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.428

Alfa AF: 0.472 Hom.: 2131

Bravo AF: 0.425

Asia WGS AF: 0.453 AC: 1573 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 09, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3831056; hg19: chr9-98997910;