Genetic Variant HSD17B3:c.453+37T>A (chr9-96251381-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000197.2(HSD17B3):c.453+37T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HSD17B3
NM_000197.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.53

Publications

9 publications found

Variant links:

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 links:

ENSG00000285269 (HGNC:):

ENSG00000285269 links:

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

HSD17B3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD17B3	NM_000197.2 link	c.453+37T>A		intron_variant	Intron 5 of 10	ENST00000375263.8	NP_000188.1	P37058-1Q6FH62
SLC35D2-HSD17B3	NR_182427.1 link	n.3220+37T>A		intron_variant	Intron 20 of 25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD17B3	ENST00000375263.8 link	c.453+37T>A		intron_variant	Intron 5 of 10	1	NM_000197.2	ENSP00000364412.3		P37058-1
ENSG00000285269	ENST00000643789.1 link	n.*2129+37T>A		intron_variant	Intron 16 of 21			ENSP00000494818.1		A0A2R8Y5X9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1432962

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

714794

African (AFR)

AF:

0.00

AC:

AN:

32876

American (AMR)

AF:

0.00

AC:

AN:

44656

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25980

East Asian (EAS)

AF:

0.00

AC:

AN:

39546

South Asian (SAS)

AF:

0.00

AC:

AN:

85666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53360

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1085738

Other (OTH)

AF:

0.00

AC:

AN:

59426

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

31009

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.34

(source)

DANN

Benign

0.52

PhyloP100

-1.5

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over