rs769496983
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_005732.4(RAD50):c.2012C>T(p.Thr671Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,196 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T671S) 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.2012C>T | p.Thr671Ile | missense_variant | 13/25 | ENST00000378823.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD50 | ENST00000378823.8 | c.2012C>T | p.Thr671Ile | missense_variant | 13/25 | 1 | NM_005732.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251304Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135828
GnomAD4 exome Cov.: 30
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74342
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 14, 2023 | The c.2012C>T (p.T671I) alteration is located in exon 13 (coding exon 13) of the RAD50 gene. This alteration results from a C to T substitution at nucleotide position 2012, causing the threonine (T) at amino acid position 671 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 21, 2023 | ClinVar contains an entry for this variant (Variation ID: 580212). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is present in population databases (rs769496983, gnomAD 0.007%). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 671 of the RAD50 protein (p.Thr671Ile). 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 not expected to disrupt RAD50 protein function. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at