1-119415482-G-GT
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000198.4(HSD3B2):c.65dup(p.Leu22PhefsTer27) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,772 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
HSD3B2
NM_000198.4 frameshift
NM_000198.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.0500
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 66 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-119415482-G-GT is Pathogenic according to our data. Variant chr1-119415482-G-GT is described in ClinVar as [Pathogenic]. Clinvar id is 1451900.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSD3B2 | NM_000198.4 | c.65dup | p.Leu22PhefsTer27 | frameshift_variant | 2/4 | ENST00000369416.4 | |
HSD3B2 | NM_001166120.2 | c.65dup | p.Leu22PhefsTer27 | frameshift_variant | 2/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSD3B2 | ENST00000369416.4 | c.65dup | p.Leu22PhefsTer27 | frameshift_variant | 2/4 | 1 | NM_000198.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152154Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251202Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135762
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461618Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727130
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 28, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1451900). This variant has not been reported in the literature in individuals affected with HSD3B2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Leu22Phefs*27) in the HSD3B2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HSD3B2 are known to be pathogenic (PMID: 11196452). - |
3 beta-Hydroxysteroid dehydrogenase deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Clinical Biochemistry Laboratory, Health Services Laboratory | Nov 20, 2023 | ACMG:PVS1 PM2 PP3 PP4 - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at