chr1-119415454-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM2PP3PP5_ModerateBP4
The NM_000198.4(HSD3B2):c.35G>A(p.Gly12Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000204 in 1,613,900 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 Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. G12G) has been classified as Likely benign.
Frequency
Consequence
NM_000198.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HSD3B2 | NM_000198.4 | c.35G>A | p.Gly12Glu | missense_variant | 2/4 | ENST00000369416.4 | |
HSD3B2 | NM_001166120.2 | c.35G>A | p.Gly12Glu | missense_variant | 2/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HSD3B2 | ENST00000369416.4 | c.35G>A | p.Gly12Glu | missense_variant | 2/4 | 1 | NM_000198.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000210 AC: 32AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251190Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135756
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461706Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727164
GnomAD4 genome ? AF: 0.000210 AC: 32AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74356
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 19, 2022 | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individuals with congenital adrenal hyperplasia (PMID: 26079780). This variant is present in population databases (rs756607591, gnomAD 0.003%). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 12 of the HSD3B2 protein (p.Gly12Glu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at