rs780080251
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_058216.3(RAD51C):βc.1013_1024delβ(p.Leu338_Lys342delinsGln) variant causes a inframe deletion, splice region change. The variant allele was found at a frequency of 0.000000685 in 1,460,670 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ). Synonymous variant affecting the same amino acid position (i.e. L338L) has been classified as Likely benign.
Frequency
Consequence
NM_058216.3 inframe_deletion, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAD51C | NM_058216.3 | c.1013_1024del | p.Leu338_Lys342delinsGln | inframe_deletion, splice_region_variant | 8/9 | ENST00000337432.9 | |
LOC105371843 | XR_007065866.1 | n.81-8117_81-8106del | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD51C | ENST00000337432.9 | c.1013_1024del | p.Leu338_Lys342delinsGln | inframe_deletion, splice_region_variant | 8/9 | 1 | NM_058216.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251400Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135866
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460670Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 726726
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Sep 21, 2021 | This missense variant replaces 5 amino acids at codon 338 to 342 of the RAD51C protein with a glutamine. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251400 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 23, 2019 | The c.1013_1024del12 variant (also known as p.L338_K342delinsQ), located in coding exon 8 of the RAD51C gene, results from an in-frame deletion of 12 nucleotides at positions 1013 to 1024. This results in the substitution of the leucine, phenylaline, glutamine, isoleucine and lysine residues for a glutamine residue at codons 338 through 342. These amino acid positions are not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Fanconi anemia complementation group O Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2022 | 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 492360). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. This variant is present in population databases (rs780080251, gnomAD 0.003%). This variant, c.1013_1024del, is a complex sequence change that results in the deletion of 5 and insertion of 1 amino acid(s) in the RAD51C protein (p.Leu338_Lys342delinsGln). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at