rs8190557

chr9-96240572-G-A

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.822+186C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,032 control chromosomes in the GnomAD database, including 1,984 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1984 hom., cov: 32)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.49

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=-0.92).
• BP6: Variant 9-96240572-G-A is Benign according to our data. Variant chr9-96240572-G-A is described in ClinVar as [Benign]. Clinvar id is 1253389.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B3	NM_000197.2	c.822+186C>T		intron_variant		ENST00000375263.8
SLC35D2-HSD17B3	NR_182427.1	n.3589+186C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B3	ENST00000375263.8	c.822+186C>T		intron_variant		1	NM_000197.2	P1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 19999 AN: 151914 Hom.: 1971 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.0861

Gnomad AMR AF: 0.0811

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0817

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0637

Gnomad OTH AF: 0.127

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.132 AC: 20040 AN: 152032 Hom.: 1984 Cov.: 32 AF XY: 0.133 AC XY: 9899 AN XY: 74330

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.0808

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0817

Gnomad4 NFE AF: 0.0637

Gnomad4 OTH AF: 0.125

Alfa AF: 0.0960 Hom.: 242

Bravo AF: 0.139

Asia WGS AF: 0.173 AC: 605 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

Oct 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.023
Dann	Benign	0.51

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: rs8190557; hg19: chr9-99002854;