1-119419495-G-A
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_000198.4(HSD3B2):c.220G>A(p.Asp74Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000617 in 1,613,814 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. D74D) has been classified as Likely benign.
Frequency
Genomes: 𝑓 0.0035 ( 7 hom., cov: 32)
Exomes 𝑓: 0.00031 ( 1 hom. )
Consequence
HSD3B2
NM_000198.4 missense
NM_000198.4 missense
Scores
1
6
11
Clinical Significance
Conservation
PhyloP100: 6.64
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 Benign. Variant got -16 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.010008693).
BP6
Variant 1-119419495-G-A is Benign according to our data. Variant chr1-119419495-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 720898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd4 at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSD3B2 | NM_000198.4 | c.220G>A | p.Asp74Asn | missense_variant | 3/4 | ENST00000369416.4 | |
HSD3B2 | NM_001166120.2 | c.220G>A | p.Asp74Asn | missense_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSD3B2 | ENST00000369416.4 | c.220G>A | p.Asp74Asn | missense_variant | 3/4 | 1 | NM_000198.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00352 AC: 536AN: 152170Hom.: 7 Cov.: 32
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GnomAD3 exomes AF: 0.000793 AC: 199AN: 250902Hom.: 0 AF XY: 0.000568 AC XY: 77AN XY: 135592
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GnomAD4 exome AF: 0.000314 AC: 459AN: 1461526Hom.: 1 Cov.: 31 AF XY: 0.000268 AC XY: 195AN XY: 727084
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GnomAD4 genome AF: 0.00352 AC: 536AN: 152288Hom.: 7 Cov.: 32 AF XY: 0.00344 AC XY: 256AN XY: 74464
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 22, 2020 | See Variant Classification Assertion Criteria. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
3 beta-Hydroxysteroid dehydrogenase deficiency Benign:2
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jun 16, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;.;L
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
P;.;P
Vest4
MVP
MPC
ClinPred
T
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at