NM_000197.2:c.607-213A>G

Variant names:

• chr9-96244607-T-C
• rs913580
• NM_000197.2:c.607-213A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000197.2(HSD17B3):​c.607-213A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,544 control chromosomes in the GnomAD database, including 18,106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.48 (18106 hom., cov: 30)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.70
• Publications: 6 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 9-96244607-T-C is Benign according to our data. Variant chr9-96244607-T-C is described in ClinVar as Benign. ClinVar VariationId is 1232739.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 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.607-213A>G		intron	N/A	NP_000188.1
	SLC35D2-HSD17B3	NR_182427.1		n.3374-213A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	ENST00000375263.8	TSL:1 MANE Select	c.607-213A>G		intron	N/A	ENSP00000364412.3
	HSD17B3	ENST00000375262.4	TSL:1	c.607-213A>G		intron	N/A	ENSP00000364411.2
	ENSG00000285269	ENST00000643789.1		n.*2283-213A>G		intron	N/A	ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 72955 AN: 151426 Hom.: 18096 Cov.: 30

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.482 AC: 72995 AN: 151544 Hom.: 18106 Cov.: 30 AF XY: 0.487 AC XY: 36042 AN XY: 74014

African (AFR) AF: 0.359 AC: 14794 AN: 41212

American (AMR) AF: 0.574 AC: 8749 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1466 AN: 3466

East Asian (EAS) AF: 0.582 AC: 3003 AN: 5158

South Asian (SAS) AF: 0.530 AC: 2547 AN: 4806

European-Finnish (FIN) AF: 0.549 AC: 5752 AN: 10478

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.517 AC: 35111 AN: 67876

Other (OTH) AF: 0.482 AC: 1008 AN: 2092

Alfa AF: 0.513 Hom.: 11245

Bravo AF: 0.476

Asia WGS AF: 0.538 AC: 1870 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.34
DANN	Benign	0.61
PhyloP100		-1.7
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: rs913580; hg19: chr9-99006889;