chr1-119415434-C-A
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000198.4(HSD3B2):c.15C>A(p.Cys5Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,613,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. C5C) has been classified as Likely benign.
Frequency
Consequence
NM_000198.4 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSD3B2 | NM_000198.4 | c.15C>A | p.Cys5Ter | stop_gained | 2/4 | ENST00000369416.4 | |
HSD3B2 | NM_001166120.2 | c.15C>A | p.Cys5Ter | stop_gained | 2/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSD3B2 | ENST00000369416.4 | c.15C>A | p.Cys5Ter | stop_gained | 2/4 | 1 | NM_000198.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152138Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 251116Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135704
GnomAD4 exome AF: 0.0000431 AC: 63AN: 1461672Hom.: 0 Cov.: 31 AF XY: 0.0000454 AC XY: 33AN XY: 727154
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152138Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74324
ClinVar
Submissions by phenotype
3 beta-Hydroxysteroid dehydrogenase deficiency Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 20, 2021 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Aug 06, 2020 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | This sequence change creates a premature translational stop signal (p.Cys5*) 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). This variant is present in population databases (rs766474996, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with 3-beta-hydroxysteroid dehydrogenase deficiency (PMID: 31611844). ClinVar contains an entry for this variant (Variation ID: 1076441). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at