chr17-58703311-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_058216.3(RAD51C):āc.687C>Gā(p.Phe229Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,611,950 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F229I) has been classified as Uncertain significance.
Frequency
Consequence
NM_058216.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAD51C | NM_058216.3 | c.687C>G | p.Phe229Leu | missense_variant | 4/9 | ENST00000337432.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD51C | ENST00000337432.9 | c.687C>G | p.Phe229Leu | missense_variant | 4/9 | 1 | NM_058216.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152130Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251196Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135776
GnomAD4 exome AF: 0.0000329 AC: 48AN: 1459820Hom.: 0 Cov.: 31 AF XY: 0.0000262 AC XY: 19AN XY: 726372
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152130Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74316
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 21, 2022 | The p.F229L variant (also known as c.687C>G), located in coding exon 4 of the RAD51C gene, results from a C to G substitution at nucleotide position 687. The phenylalanine at codon 229 is replaced by leucine, an amino acid with highly similar properties. In one study, this variant was reported in 1/45 patients with idiopathic aplastic anemia (Collopy LC et al. Haematologica. 2014 Jul;99:e109-11). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Jul 21, 2021 | This missense variant replaces phenylalanine with leucine at codon 229 of the RAD51C protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with idiopathic aplastic anemia (PMID: 24763404). This variant has been identified in 2/251196 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Jun 16, 2017 | - - |
Fanconi anemia complementation group O Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 17, 2023 | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 229 of the RAD51C protein (p.Phe229Leu). This variant is present in population databases (rs780177888, gnomAD 0.0009%). This missense change has been observed in individual(s) with aplastic anemia, but was also reported in an unaffected individual (PMID: 24763404). ClinVar contains an entry for this variant (Variation ID: 241774). 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 not expected to disrupt RAD51C protein function with a negative predictive value of 80%. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at