rs6211
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_000198.4(HSD3B2):āc.280G>Cā(p.Glu94Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000162 in 1,613,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Consequence
NM_000198.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HSD3B2 | NM_000198.4 | c.280G>C | p.Glu94Gln | missense_variant | 3/4 | ENST00000369416.4 | NP_000189.1 | |
HSD3B2 | NM_001166120.2 | c.280G>C | p.Glu94Gln | missense_variant | 3/4 | NP_001159592.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HSD3B2 | ENST00000369416.4 | c.280G>C | p.Glu94Gln | missense_variant | 3/4 | 1 | NM_000198.4 | ENSP00000358424.3 |
Frequencies
GnomAD3 genomes AF: 0.000565 AC: 86AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000207 AC: 52AN: 251032Hom.: 0 AF XY: 0.000184 AC XY: 25AN XY: 135676
GnomAD4 exome AF: 0.000119 AC: 174AN: 1461622Hom.: 0 Cov.: 31 AF XY: 0.000109 AC XY: 79AN XY: 727126
GnomAD4 genome AF: 0.000578 AC: 88AN: 152292Hom.: 0 Cov.: 32 AF XY: 0.000551 AC XY: 41AN XY: 74452
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 27, 2021 | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 94 of the HSD3B2 protein (p.Glu94Gln). This variant is present in population databases (rs6211, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with HSD3B2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2022 | HSD3B2: BP4 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at