9-96240982-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000197.2(HSD17B3):c.673-75G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 1,549,094 control chromosomes in the GnomAD database, including 556,398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.88 (59627 hom., cov: 31)
  • Exomes 𝑓: 0.84 (496771 hom.)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.63

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 9-96240982-C-T is Benign according to our data. Variant chr9-96240982-C-T is described in ClinVar as [Benign]. Clinvar id is 1291003.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B3	NM_000197.2	c.673-75G>A		intron_variant		ENST00000375263.8
SLC35D2-HSD17B3	NR_182427.1	n.3440-75G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B3	ENST00000375263.8	c.673-75G>A		intron_variant		1	NM_000197.2	P1

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134252 AN: 152042 Hom.: 59563 Cov.: 31

Gnomad AFR AF: 0.970

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.865

GnomAD4 exome AF: 0.842 AC: 1176903 AN: 1396934 Hom.: 496771 AF XY: 0.841 AC XY: 587189 AN XY: 698312

Gnomad4 AFR exome AF: 0.976

Gnomad4 AMR exome AF: 0.816

Gnomad4 ASJ exome AF: 0.840

Gnomad4 EAS exome AF: 0.849

Gnomad4 SAS exome AF: 0.777

Gnomad4 FIN exome AF: 0.906

Gnomad4 NFE exome AF: 0.841

Gnomad4 OTH exome AF: 0.849

GnomAD4 genome AF: 0.883 AC: 134376 AN: 152160 Hom.: 59627 Cov.: 31 AF XY: 0.884 AC XY: 65726 AN XY: 74388

Gnomad4 AFR AF: 0.970

Gnomad4 AMR AF: 0.857

Gnomad4 ASJ AF: 0.831

Gnomad4 EAS AF: 0.848

Gnomad4 SAS AF: 0.770

Gnomad4 FIN AF: 0.910

Gnomad4 NFE AF: 0.845

Gnomad4 OTH AF: 0.866

Alfa AF: 0.877 Hom.: 7344

Bravo AF: 0.884

Asia WGS AF: 0.818 AC: 2847 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

Mar 03, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.36
Dann	Benign	0.61

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: rs2066485; hg19: chr9-99003264;