rs1119864

Variant names:

• chr9-96292322-T-C
• rs1119864
• NM_000197.2:c.201+6094A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

HSD17B3 Gene-Disease associations (from GenCC):

• 46,XY disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase 3 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000285269 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.201+6094A>G		intron_variant	Intron 2 of 10	ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.2968+6094A>G		intron_variant	Intron 17 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.201+6094A>G		intron_variant	Intron 2 of 10	1	NM_000197.2	ENSP00000364412.3
ENSG00000285269	ENST00000643789.1	n.*1877+6094A>G		intron_variant	Intron 13 of 21			ENSP00000494818.1

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

African (AFR) AF: 0.228 AC: 9468 AN: 41466

American (AMR) AF: 0.237 AC: 3618 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1052 AN: 3472

East Asian (EAS) AF: 0.0616 AC: 319 AN: 5182

South Asian (SAS) AF: 0.123 AC: 593 AN: 4826

European-Finnish (FIN) AF: 0.313 AC: 3307 AN: 10574

Middle Eastern (MID) AF: 0.212 AC: 62 AN: 292

European-Non Finnish (NFE) AF: 0.354 AC: 24093 AN: 67968

Other (OTH) AF: 0.283 AC: 596 AN: 2108

Alfa AF: 0.328 Hom.: 26664

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
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1119864; hg19: chr9-99054604;