NM_000197.2:c.202-17961A>T

Variant names:

• chr9-96272904-T-A
• rs13302476
• NM_000197.2:c.202-17961A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000197.2(HSD17B3):​c.202-17961A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,034 control chromosomes in the GnomAD database, including 3,602 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 0.20 (3602 hom., cov: 31)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000197.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	NM_000197.2	MANE Select	c.202-17961A>T		intron	N/A	NP_000188.1
	SLC35D2-HSD17B3	NR_182427.1		n.2969-17961A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	ENST00000375263.8	TSL:1 MANE Select	c.202-17961A>T		intron	N/A	ENSP00000364412.3
	HSD17B3	ENST00000375262.4	TSL:1	c.202-17961A>T		intron	N/A	ENSP00000364411.2
	ENSG00000285269	ENST00000643789.1		n.*1878-17961A>T		intron	N/A	ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30148 AN: 151916 Hom.: 3601 Cov.: 31

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.0692

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.199 AC: 30196 AN: 152034 Hom.: 3602 Cov.: 31 AF XY: 0.203 AC XY: 15118 AN XY: 74342

African (AFR) AF: 0.243 AC: 10060 AN: 41462

American (AMR) AF: 0.215 AC: 3285 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 542 AN: 3472

East Asian (EAS) AF: 0.561 AC: 2895 AN: 5158

South Asian (SAS) AF: 0.308 AC: 1481 AN: 4816

European-Finnish (FIN) AF: 0.156 AC: 1644 AN: 10568

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9698 AN: 67974

Other (OTH) AF: 0.215 AC: 453 AN: 2108

Alfa AF: 0.0672 Hom.: 70

Bravo AF: 0.206

Asia WGS AF: 0.394 AC: 1371 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.22
DANN	Benign	0.37
PhyloP100		-1.3
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: rs13302476; hg19: chr9-99035186;