dbSNP rs116449508: HSD3B2:p.Gly2Asp (chr1-119415424-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000198.4(HSD3B2):c.5G>A(p.Gly2Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. G2V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

HSD3B2
NM_000198.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.01

Publications

3 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.5G>A	p.Gly2Asp	missense	Exon 2 of 4	NP_000189.1	P26439-1
	HSD3B2	NM_001166120.2		c.5G>A	p.Gly2Asp	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.5G>A	p.Gly2Asp	missense	Exon 2 of 4	ENSP00000358424.3	P26439-1
HSD3B2	ENST00000543831.5	TSL:3	c.5G>A	p.Gly2Asp	missense	Exon 2 of 4	ENSP00000445122.1	P26439-1
HSD3B2	ENST00000902254.1		c.5G>A	p.Gly2Asp	missense	Exon 1 of 3	ENSP00000572313.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.064

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.42

Eigen

Benign

-0.0036

Eigen_PC

Benign

-0.14

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.51

M_CAP

Uncertain

0.23

MetaRNN

Uncertain

0.73

MetaSVM

Uncertain

-0.25

MutationAssessor

Benign

1.8

PhyloP100

1.0

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-4.8

REVEL

Uncertain

0.41

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.21

MutPred

0.55

Loss of catalytic residue at W3 (P = 0.0705)

MVP

0.99

MPC

1.0

ClinPred

0.99

GERP RS

2.7

PromoterAI

-0.039

Neutral

(source)

Varity_R

0.57

gMVP

0.31

Mutation Taster

=91/9

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