rs7039978

Positions:

• chr9-96259300-A-G
• chr9-96259300-A-T

Variant summary

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

The NM_000197.2(HSD17B3):​c.202-4357T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 152,046 control chromosomes in the GnomAD database, including 26,400 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 0.57 (26400 hom., cov: 32)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.202-4357T>C		intron_variant		ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.2969-4357T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.202-4357T>C		intron_variant		1	NM_000197.2	ENSP00000364412	P1

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86360 AN: 151928 Hom.: 26359 Cov.: 32

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.569 AC: 86456 AN: 152046 Hom.: 26400 Cov.: 32 AF XY: 0.555 AC XY: 41243 AN XY: 74322

Gnomad4 AFR AF: 0.791

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.520

Gnomad4 OTH AF: 0.563

Alfa AF: 0.526 Hom.: 19549

Bravo AF: 0.582

Asia WGS AF: 0.337 AC: 1177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.81
DANN	Benign	0.63

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: rs7039978; hg19: chr9-99021582;