9-96253813-T-G

Position:

• chr9-96253813-T-G

Variant summary

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

The NM_000197.2(HSD17B3):​c.278-903A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,024 control chromosomes in the GnomAD database, including 33,995 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 0.66 (33995 hom., cov: 31)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.278-903A>C		intron_variant		ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.3045-903A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.278-903A>C		intron_variant		1	NM_000197.2	ENSP00000364412	P1

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100836 AN: 151906 Hom.: 33972 Cov.: 31

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.625

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.664 AC: 100906 AN: 152024 Hom.: 33995 Cov.: 31 AF XY: 0.665 AC XY: 49378 AN XY: 74290

Gnomad4 AFR AF: 0.747

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.625

Gnomad4 EAS AF: 0.718

Gnomad4 SAS AF: 0.596

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.629

Alfa AF: 0.626 Hom.: 40630

Bravo AF: 0.654

Asia WGS AF: 0.657 AC: 2287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.16
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2026001; hg19: chr9-99016095;