9-96240473-C-G

Variant names:

• chr9-96240473-C-G
• rs1927882
• NM_000197.2:c.822+285G>C

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.822+285G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 151,996 control chromosomes in the GnomAD database, including 28,894 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.61 (28894 hom., cov: 32)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.67
• Publications: 1 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=-0.87).
• BP6: Variant 9-96240473-C-G is Benign according to our data. Variant chr9-96240473-C-G is described in ClinVar as Benign. ClinVar VariationId is 1273772.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.822+285G>C		intron_variant	Intron 10 of 10	ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.3589+285G>C		intron_variant	Intron 25 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.822+285G>C		intron_variant	Intron 10 of 10	1	NM_000197.2	ENSP00000364412.3
ENSG00000285269	ENST00000643789.1	n.*2498+285G>C		intron_variant	Intron 21 of 21			ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93361 AN: 151878 Hom.: 28863 Cov.: 32

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.615 AC: 93442 AN: 151996 Hom.: 28894 Cov.: 32 AF XY: 0.622 AC XY: 46165 AN XY: 74280

African (AFR) AF: 0.643 AC: 26630 AN: 41446

American (AMR) AF: 0.651 AC: 9940 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1922 AN: 3472

East Asian (EAS) AF: 0.820 AC: 4220 AN: 5146

South Asian (SAS) AF: 0.637 AC: 3066 AN: 4812

European-Finnish (FIN) AF: 0.625 AC: 6603 AN: 10568

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.575 AC: 39099 AN: 67962

Other (OTH) AF: 0.604 AC: 1276 AN: 2112

Alfa AF: 0.488 Hom.: 1401

Bravo AF: 0.618

Asia WGS AF: 0.711 AC: 2472 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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.16
DANN	Benign	0.46
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: rs1927882; hg19: chr9-99002755;