rs80358218
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM4PP5
The NM_000198.4(HSD3B2):āc.1119A>Cā(p.Ter373CysextTer95) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 31)
Exomes š: 0.0000075 ( 0 hom. )
Consequence
HSD3B2
NM_000198.4 stop_lost
NM_000198.4 stop_lost
Scores
2
1
4
Clinical Significance
Conservation
PhyloP100: 3.52
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Stoplost variant in NM_000198.4 Downstream stopcodon found after 419 codons.
PP5
?
Variant 1-119422620-A-C is Pathogenic according to our data. Variant chr1-119422620-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 12189.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSD3B2 | NM_000198.4 | c.1119A>C | p.Ter373CysextTer95 | stop_lost | 4/4 | ENST00000369416.4 | |
HSD3B2 | NM_001166120.2 | c.1119A>C | p.Ter373CysextTer95 | stop_lost | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSD3B2 | ENST00000369416.4 | c.1119A>C | p.Ter373CysextTer95 | stop_lost | 4/4 | 1 | NM_000198.4 | P1 | |
HSD3B2 | ENST00000543831.5 | c.1119A>C | p.Ter373CysextTer95 | stop_lost | 4/4 | 3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
1
AN:
152198
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249092Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134794
GnomAD3 exomes
AF:
AC:
1
AN:
249092
Hom.:
AF XY:
AC XY:
1
AN XY:
134794
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461538Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727080
GnomAD4 exome
AF:
AC:
11
AN:
1461538
Hom.:
Cov.:
31
AF XY:
AC XY:
6
AN XY:
727080
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152198Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74352
GnomAD4 genome
?
AF:
AC:
1
AN:
152198
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
74352
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
3 beta-Hydroxysteroid dehydrogenase deficiency Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2002 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at