rs557802139
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_005732.4(RAD50):c.1289A>T(p.Asp430Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000416 in 1,608,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. D430D) has been classified as Likely benign.
Frequency
Consequence
NM_005732.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAD50 | NM_005732.4 | c.1289A>T | p.Asp430Val | missense_variant | 9/25 | ENST00000378823.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD50 | ENST00000378823.8 | c.1289A>T | p.Asp430Val | missense_variant | 9/25 | 1 | NM_005732.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000100 AC: 25AN: 248772Hom.: 0 AF XY: 0.000126 AC XY: 17AN XY: 134662
GnomAD4 exome AF: 0.0000433 AC: 63AN: 1456466Hom.: 0 Cov.: 31 AF XY: 0.0000676 AC XY: 49AN XY: 724322
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152316Hom.: 0 Cov.: 32 AF XY: 0.0000268 AC XY: 2AN XY: 74490
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 19, 2023 | The c.1289A>T (p.D430V) alteration is located in exon 9 (coding exon 9) of the RAD50 gene. This alteration results from a A to T substitution at nucleotide position 1289, causing the aspartic acid (D) at amino acid position 430 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 22, 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: 408365). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is present in population databases (rs557802139, gnomAD 0.08%). This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 430 of the RAD50 protein (p.Asp430Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at