rs2066485

Variant names:

• chr9-96240982-C-T
• rs2066485
• NM_000197.2:c.673-75G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-96240982-C-T
• chr9-96240982-C-A
• chr9-96240982-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000197.2(HSD17B3):​c.673-75G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 1,549,094 control chromosomes in the GnomAD database, including 556,398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (59627 hom., cov: 31)
  • Exomes 𝑓: 0.84 (496771 hom.)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.63
• Publications: 11 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet

ENSG00000285269 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 9-96240982-C-T is Benign according to our data. Variant chr9-96240982-C-T is described in ClinVar as Benign. ClinVar VariationId is 1291003.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.962 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	NM_000197.2	MANE Select	c.673-75G>A		intron	N/A	NP_000188.1	P37058-1
	SLC35D2-HSD17B3	NR_182427.1		n.3440-75G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSD17B3	ENST00000375263.8	TSL:1 MANE Select	c.673-75G>A		intron	N/A	ENSP00000364412.3	P37058-1
	HSD17B3	ENST00000375262.4	TSL:1	c.672+3347G>A		intron	N/A	ENSP00000364411.2	P37058-2
	ENSG00000285269	ENST00000643789.1		n.*2349-75G>A		intron	N/A	ENSP00000494818.1	A0A2R8Y5X9

Frequencies

GnomAD3 genomes AF: 0.883 AC: 134252 AN: 152042 Hom.: 59563 Cov.: 31

Gnomad AFR AF: 0.970

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.865

GnomAD4 exome AF: 0.842 AC: 1176903 AN: 1396934 Hom.: 496771 AF XY: 0.841 AC XY: 587189 AN XY: 698312

African (AFR) AF: 0.976 AC: 31407 AN: 32194

American (AMR) AF: 0.816 AC: 36232 AN: 44412

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 21611 AN: 25724

East Asian (EAS) AF: 0.849 AC: 33408 AN: 39362

South Asian (SAS) AF: 0.777 AC: 65986 AN: 84886

European-Finnish (FIN) AF: 0.906 AC: 44838 AN: 49486

Middle Eastern (MID) AF: 0.836 AC: 4720 AN: 5648

European-Non Finnish (NFE) AF: 0.841 AC: 889210 AN: 1056948

Other (OTH) AF: 0.849 AC: 49491 AN: 58274

GnomAD4 genome AF: 0.883 AC: 134376 AN: 152160 Hom.: 59627 Cov.: 31 AF XY: 0.884 AC XY: 65726 AN XY: 74388

African (AFR) AF: 0.970 AC: 40302 AN: 41542

American (AMR) AF: 0.857 AC: 13098 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2882 AN: 3468

East Asian (EAS) AF: 0.848 AC: 4380 AN: 5164

South Asian (SAS) AF: 0.770 AC: 3691 AN: 4792

European-Finnish (FIN) AF: 0.910 AC: 9656 AN: 10608

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.845 AC: 57480 AN: 67986

Other (OTH) AF: 0.866 AC: 1823 AN: 2106

Alfa AF: 0.877 Hom.: 7344

Bravo AF: 0.884

Asia WGS AF: 0.818 AC: 2847 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.36
DANN	Benign	0.61
PhyloP100		-1.6
Mutation Taster		=15/85	disease causing

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: rs2066485; hg19: chr9-99003264;