rs763343833
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_005732.4(RAD50):āc.1594A>Gā(p.Thr532Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,660 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 (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T532I) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAD50 | NM_005732.4 | c.1594A>G | p.Thr532Ala | missense_variant | 10/25 | ENST00000378823.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD50 | ENST00000378823.8 | c.1594A>G | p.Thr532Ala | missense_variant | 10/25 | 1 | NM_005732.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000800 AC: 2AN: 249928Hom.: 0 AF XY: 0.00000740 AC XY: 1AN XY: 135186
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461660Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727124
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 14, 2023 | 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 RAD50 protein function. 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. ClinVar contains an entry for this variant (Variation ID: 580051). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 532 of the RAD50 protein (p.Thr532Ala). This variant is present in population databases (rs763343833, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 25, 2023 | The p.T532A variant (also known as c.1594A>G), located in coding exon 10 of the RAD50 gene, results from an A to G substitution at nucleotide position 1594. The threonine at codon 532 is replaced by alanine, an amino acid with 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