NM_000198.4:c.12C>A

Variant names:

• chr1-119415431-C-A
• NM_000198.4:c.12C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000198.4(HSD3B2):​c.12C>A​(p.Ser4Arg) 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 1,461,650 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. Synonymous variant affecting the same amino acid position (i.e. S4S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: HSD3B2 NM_000198.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40499085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD3B2	NM_000198.4	c.12C>A	p.Ser4Arg	missense_variant	Exon 2 of 4	ENST00000369416.4	NP_000189.1
HSD3B2	NM_001166120.2	c.12C>A	p.Ser4Arg	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.12C>A	p.Ser4Arg	missense_variant	Exon 2 of 4	1	NM_000198.4	ENSP00000358424.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461650 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727146

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Uncertain	0.018	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.091
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.76	T;T;.
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Benign	-0.43	T
MutationAssessor	Benign	-0.10	N;.;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.5	N;N;N
REVEL	Uncertain	0.46
Sift	Benign	0.22	T;T;T
Sift4G	Benign	0.092	T;T;T
Polyphen		0.021	B;.;B
Vest4		0.19
MutPred		0.44		Gain of MoRF binding (P = 2e-04);Gain of MoRF binding (P = 2e-04);Gain of MoRF binding (P = 2e-04);
MVP		1.0
MPC		0.32
ClinPred		0.67	D
GERP RS		3.6
Varity_R		0.26
gMVP		0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-119958054;