rs1119864

Positions:

• chr9-96292322-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000197.2(HSD17B3):​c.201+6094A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,082 control chromosomes in the GnomAD database, including 6,719 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (6719 hom., cov: 32)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HSD17B3	NM_000197.2	c.201+6094A>G		intron_variant		ENST00000375263.8
SLC35D2-HSD17B3	NR_182427.1	n.2968+6094A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HSD17B3	ENST00000375263.8	c.201+6094A>G		intron_variant		1	NM_000197.2	P1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43578 AN: 151962 Hom.: 6713 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.0616

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.287 AC: 43602 AN: 152082 Hom.: 6719 Cov.: 32 AF XY: 0.279 AC XY: 20717 AN XY: 74370

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.0616

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.283

Alfa AF: 0.333 Hom.: 11877

Bravo AF: 0.279

Asia WGS AF: 0.101 AC: 352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.60

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: rs1119864; hg19: chr9-99054604;