9-96255802-C-T

Position:

• chr9-96255802-C-T

Variant summary

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

The NM_000197.2(HSD17B3):​c.202-859G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 152,122 control chromosomes in the GnomAD database, including 49,052 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 0.80 (49052 hom., cov: 31)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.869

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.938 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.202-859G>A		intron_variant		ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.2969-859G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.202-859G>A		intron_variant		1	NM_000197.2	ENSP00000364412	P1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121171 AN: 152004 Hom.: 48986 Cov.: 31

Gnomad AFR AF: 0.945

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.792

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

GnomAD4 genome AF: 0.797 AC: 121296 AN: 152122 Hom.: 49052 Cov.: 31 AF XY: 0.795 AC XY: 59081 AN XY: 74354

Gnomad4 AFR AF: 0.945

Gnomad4 AMR AF: 0.800

Gnomad4 ASJ AF: 0.751

Gnomad4 EAS AF: 0.717

Gnomad4 SAS AF: 0.712

Gnomad4 FIN AF: 0.718

Gnomad4 NFE AF: 0.735

Gnomad4 OTH AF: 0.793

Alfa AF: 0.768 Hom.: 8395

Bravo AF: 0.809

Asia WGS AF: 0.746 AC: 2597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.34
DANN	Benign	0.48

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: rs2479824; hg19: chr9-99018084;