NM_000197.2:c.201+20197A>C

Variant names:

• chr9-96278219-T-G
• rs1983828
• NM_000197.2:c.201+20197A>C

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+20197A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,102 control chromosomes in the GnomAD database, including 6,817 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 0.28 (6817 hom., cov: 32)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.500
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.201+20197A>C		intron_variant	Intron 2 of 10	ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.2968+20197A>C		intron_variant	Intron 17 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.201+20197A>C		intron_variant	Intron 2 of 10	1	NM_000197.2	ENSP00000364412.3
ENSG00000285269	ENST00000643789.1	n.*1877+20197A>C		intron_variant	Intron 13 of 21			ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42572 AN: 151982 Hom.: 6817 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.0662

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.280 AC: 42574 AN: 152102 Hom.: 6817 Cov.: 32 AF XY: 0.272 AC XY: 20224 AN XY: 74352

African (AFR) AF: 0.167 AC: 6917 AN: 41482

American (AMR) AF: 0.244 AC: 3737 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1082 AN: 3470

East Asian (EAS) AF: 0.0661 AC: 343 AN: 5186

South Asian (SAS) AF: 0.123 AC: 594 AN: 4818

European-Finnish (FIN) AF: 0.330 AC: 3485 AN: 10558

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25283 AN: 67980

Other (OTH) AF: 0.269 AC: 569 AN: 2112

Alfa AF: 0.333 Hom.: 34086

Bravo AF: 0.269

Asia WGS AF: 0.106 AC: 371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.54
PhyloP100		0.50
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: rs1983828; hg19: chr9-99040501;