NM_000198.4:c.5G>A

Variant names:

• chr1-119415424-G-A
• rs116449508
• NM_000198.4:c.5G>A

Variant summary

Our verdict is Uncertain significance. Variant got 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD3B2	NM_000198.4	c.5G>A	p.Gly2Asp	missense_variant	Exon 2 of 4	ENST00000369416.4	NP_000189.1
HSD3B2	NM_001166120.2	c.5G>A	p.Gly2Asp	missense_variant	Exon 2 of 4		NP_001159592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD3B2	ENST00000369416.4	c.5G>A	p.Gly2Asp	missense_variant	Exon 2 of 4	1	NM_000198.4	ENSP00000358424.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.42	T;T;T
Eigen	Benign	-0.0036
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.51	T;T;.
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.73	D;D;D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Benign	1.8	L;.;L
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-4.8	D;D;D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.21
MutPred		0.55		Loss of catalytic residue at W3 (P = 0.0705);Loss of catalytic residue at W3 (P = 0.0705);Loss of catalytic residue at W3 (P = 0.0705);
MVP		0.99
MPC		1.0
ClinPred		0.99	D
GERP RS		2.7
Varity_R		0.57
gMVP		0.31

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

LitVar

Other links and lift over

dbSNP: rs116449508; hg19: chr1-119958047; COSMIC: COSV105924463; COSMIC: COSV105924463;