rs1060502604
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM1BP4
The NM_058216.3(RAD51C):c.550G>A(p.Ala184Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A184A) has been classified as Likely benign.
Frequency
Consequence
NM_058216.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAD51C | NM_058216.3 | c.550G>A | p.Ala184Thr | missense_variant | 3/9 | ENST00000337432.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD51C | ENST00000337432.9 | c.550G>A | p.Ala184Thr | missense_variant | 3/9 | 1 | NM_058216.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251468Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135906
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461852Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727234
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 29, 2019 | - - |
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Mar 16, 2022 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 04, 2023 | The p.A184T variant (also known as c.550G>A), located in coding exon 3 of the RAD51C gene, results from a G to A substitution at nucleotide position 550. The alanine at codon 184 is replaced by threonine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 10, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 14704354) - |
Fanconi anemia complementation group O Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 29, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 184 of the RAD51C protein (p.Ala184Thr). This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. ClinVar contains an entry for this variant (Variation ID: 409864). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RAD51C 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. - |
Breast-ovarian cancer, familial, susceptibility to, 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetics and Molecular Pathology, SA Pathology | Feb 08, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at