rs587743300

Variant names:

• chr1-119507514-G-A
• NM_000862.3:c.38G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-119507514-G-A
• chr1-119507514-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_000862.3(HSD3B1):​c.38G>A​(p.Gly13Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. G13V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HSD3B1 NM_000862.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.73

Genes affected

HSD3B1 (HGNC:5217): (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1) The protein encoded by this gene is an enzyme that catalyzes the oxidative conversion of delta-5-3-beta-hydroxysteroid precursors into delta-4-ketosteroids, which leads to the production of all classes of steroid hormones. The encoded protein also catalyzes the interconversion of 3-beta-hydroxy- and 3-keto-5-alpha-androstane steroids. [provided by RefSeq, Jun 2016]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.965

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HSD3B1	NM_000862.3	c.38G>A	p.Gly13Glu	missense_variant	Exon 2 of 4	ENST00000369413.8	NP_000853.1
HSD3B1	NM_001328615.1	c.38G>A	p.Gly13Glu	missense_variant	Exon 2 of 4		NP_001315544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HSD3B1	ENST00000369413.8	c.38G>A	p.Gly13Glu	missense_variant	Exon 2 of 4	1	NM_000862.3	ENSP00000358421.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.54	D
BayesDel_noAF	Pathogenic	0.53
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.86	D;D;D
Eigen	Pathogenic	0.70
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.94	D;.;D
M_CAP	Uncertain	0.21	D
MetaRNN	Pathogenic	0.97	D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	4.2	.;H;H
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-6.8	D;D;D
REVEL	Pathogenic	0.92
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.97, 0.96
MVP		0.98
MPC		0.23
ClinPred		1.0	D
GERP RS		2.9
Varity_R		0.94
gMVP		0.83

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: chr1-120050137;