chr5-132640798-C-A
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_005732.4(RAD50):c.3745C>A(p.Leu1249Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L1249P) has been classified as Uncertain significance.
Frequency
Consequence
NM_005732.4 missense
Scores
Clinical Significance
Conservation
Publications
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ACMG classification
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RAD50 | NM_005732.4 | c.3745C>A | p.Leu1249Met | missense_variant | Exon 24 of 25 | ENST00000378823.8 | NP_005723.2 | |
TH2LCRR | NR_132124.1 | n.45+948G>T | intron_variant | Intron 1 of 2 | ||||
TH2LCRR | NR_132125.1 | n.189+1400G>T | intron_variant | Intron 2 of 2 | ||||
TH2LCRR | NR_132126.1 | n.175-2533G>T | intron_variant | Intron 1 of 1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RAD50 | ENST00000378823.8 | c.3745C>A | p.Leu1249Met | missense_variant | Exon 24 of 25 | 1 | NM_005732.4 | ENSP00000368100.4 | ||
ENSG00000283782 | ENST00000638452.2 | c.3448C>A | p.Leu1150Met | missense_variant | Exon 26 of 27 | 5 | ENSP00000492349.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
The p.L1249M variant (also known as c.3745C>A), located in coding exon 24 of the RAD50 gene, results from a C to A substitution at nucleotide position 3745. The leucine at codon 1249 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at