chr9-96251381-A-G

Variant names:

• chr9-96251381-A-G
• rs408876
• NM_000197.2:c.453+37T>C

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.453+37T>C 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 1,584,216 control chromosomes in the GnomAD database, including 568,629 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (59222 hom., cov: 32)
  • Exomes 𝑓: 0.84 (509407 hom.)
• Consequence: HSD17B3 NM_000197.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.53
• Publications: 9 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]

ENSG00000285269 (HGNC:):

HSD17B3-AS1 (HGNC:53136): (HSD17B3 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-96251381-A-G is Benign according to our data. Variant chr9-96251381-A-G is described in ClinVar as Benign. ClinVar VariationId is 255509.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2	c.453+37T>C		intron_variant	Intron 5 of 10	ENST00000375263.8	NP_000188.1
SLC35D2-HSD17B3	NR_182427.1	n.3220+37T>C		intron_variant	Intron 20 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8	c.453+37T>C		intron_variant	Intron 5 of 10	1	NM_000197.2	ENSP00000364412.3
ENSG00000285269	ENST00000643789.1	n.*2129+37T>C		intron_variant	Intron 16 of 21			ENSP00000494818.1

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133873 AN: 152122 Hom.: 59160 Cov.: 32

Gnomad AFR AF: 0.959

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.910

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.845

Gnomad OTH AF: 0.866

GnomAD2 exomes AF: 0.844 AC: 211833 AN: 250888 AF XY: 0.840

Gnomad AFR exome AF: 0.962

Gnomad AMR exome AF: 0.810

Gnomad ASJ exome AF: 0.838

Gnomad EAS exome AF: 0.847

Gnomad FIN exome AF: 0.904

Gnomad NFE exome AF: 0.845

Gnomad OTH exome AF: 0.847

GnomAD4 exome AF: 0.843 AC: 1206649 AN: 1431976 Hom.: 509407 Cov.: 25 AF XY: 0.841 AC XY: 600795 AN XY: 714308

African (AFR) AF: 0.966 AC: 31743 AN: 32868

American (AMR) AF: 0.815 AC: 36381 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 21816 AN: 25976

East Asian (EAS) AF: 0.849 AC: 33589 AN: 39542

South Asian (SAS) AF: 0.778 AC: 66635 AN: 85636

European-Finnish (FIN) AF: 0.906 AC: 48326 AN: 53344

Middle Eastern (MID) AF: 0.833 AC: 4754 AN: 5710

European-Non Finnish (NFE) AF: 0.842 AC: 913040 AN: 1084870

Other (OTH) AF: 0.848 AC: 50365 AN: 59380

GnomAD4 genome AF: 0.880 AC: 133995 AN: 152240 Hom.: 59222 Cov.: 32 AF XY: 0.881 AC XY: 65561 AN XY: 74422

African (AFR) AF: 0.959 AC: 39858 AN: 41554

American (AMR) AF: 0.856 AC: 13099 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2888 AN: 3472

East Asian (EAS) AF: 0.849 AC: 4396 AN: 5178

South Asian (SAS) AF: 0.771 AC: 3721 AN: 4824

European-Finnish (FIN) AF: 0.910 AC: 9642 AN: 10592

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.845 AC: 57495 AN: 68008

Other (OTH) AF: 0.867 AC: 1834 AN: 2116

Alfa AF: 0.851 Hom.: 31009

Bravo AF: 0.880

Asia WGS AF: 0.819 AC: 2849 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

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	-0.83
CADD	Benign	0.40
DANN	Benign	0.34
PhyloP100		-1.5
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: rs408876; hg19: chr9-99013663;