rs377415802
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_005732.4(RAD50):āc.3601T>Cā(p.Cys1201Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. C1201G) has been classified as Uncertain significance.
Frequency
Consequence
NM_005732.4 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 |
---|---|---|---|---|---|---|---|
RAD50 | NM_005732.4 | c.3601T>C | p.Cys1201Arg | missense_variant | 23/25 | ENST00000378823.8 | |
TH2LCRR | NR_132124.1 | n.105A>G | non_coding_transcript_exon_variant | 2/3 | |||
TH2LCRR | NR_132125.1 | n.249A>G | non_coding_transcript_exon_variant | 3/3 | |||
TH2LCRR | NR_132126.1 | n.234A>G | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD50 | ENST00000378823.8 | c.3601T>C | p.Cys1201Arg | missense_variant | 23/25 | 1 | NM_005732.4 | P1 | |
TH2LCRR | ENST00000435042.1 | n.342A>G | non_coding_transcript_exon_variant | 4/4 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251334Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135838
GnomAD4 exome AF: 0.0000342 AC: 50AN: 1461878Hom.: 0 Cov.: 31 AF XY: 0.0000344 AC XY: 25AN XY: 727238
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74336
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 31, 2023 | 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. 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 RAD50 protein function. ClinVar contains an entry for this variant (Variation ID: 185730). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is present in population databases (rs377415802, gnomAD 0.007%). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 1201 of the RAD50 protein (p.Cys1201Arg). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 18, 2022 | The p.C1201R variant (also known as c.3601T>C), located in coding exon 23 of the RAD50 gene, results from a T to C substitution at nucleotide position 3601. The cysteine at codon 1201 is replaced by arginine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious 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