dbSNP rs139191056: HSD3B2:p.Arg20Ser (chr1-119415477-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_000198.4(HSD3B2):c.58C>A(p.Arg20Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R20C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HSD3B2
NM_000198.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.270

Publications

0 publications found

Variant links:

Genes affected

HSD3B2 (HGNC:5218): (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2) The protein encoded by this gene is a bifunctional enzyme that catalyzes the oxidative conversion of delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. It plays a crucial role in the biosynthesis of all classes of hormonal steroids. This gene is predominantly expressed in the adrenals and the gonads. Mutations in this gene are associated with 3-beta-hydroxysteroid dehydrogenase, type II, deficiency. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Oct 2009]

HSD3B2 Gene-Disease associations (from GenCC):

congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

HSD3B2 links:

ENSG00000307032 (HGNC:):

ENSG00000307032 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3562367).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000198.4. 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
	HSD3B2	NM_000198.4	MANE Select	c.58C>A	p.Arg20Ser	missense	Exon 2 of 4	NP_000189.1	P26439-1
	HSD3B2	NM_001166120.2		c.58C>A	p.Arg20Ser	missense	Exon 2 of 4	NP_001159592.1	P26439-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HSD3B2	ENST00000369416.4	TSL:1 MANE Select	c.58C>A	p.Arg20Ser	missense	Exon 2 of 4	ENSP00000358424.3	P26439-1
HSD3B2	ENST00000543831.5	TSL:3	c.58C>A	p.Arg20Ser	missense	Exon 2 of 4	ENSP00000445122.1	P26439-1
HSD3B2	ENST00000902254.1		c.58C>A	p.Arg20Ser	missense	Exon 1 of 3	ENSP00000572313.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461674

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727148

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111874

Other (OTH)

AF:

0.00

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Uncertain

0.018

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Uncertain

0.71

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.58

M_CAP

Uncertain

0.092

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.65

MutationAssessor

Benign

1.8

PhyloP100

0.27

PrimateAI

Benign

0.19

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.35

Sift

Benign

0.041

Sift4G

Uncertain

0.046

Polyphen

0.26

Vest4

0.13

MutPred

0.62

Gain of phosphorylation at R20 (P = 0.0404)

MVP

0.95

MPC

0.30

ClinPred

0.33

GERP RS

0.20

PromoterAI

0.011

Neutral

(source)

Varity_R

0.16

gMVP

0.28

Mutation Taster

=80/20

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over