rs1554100868
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_005732.4(RAD50):āc.3464A>Cā(p.Tyr1155Ser) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 32)
Exomes š: 0.0000034 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
RAD50
NM_005732.4 missense
NM_005732.4 missense
Scores
10
4
3
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 8.93
Genes affected
RAD50 (HGNC:9816): (RAD50 double strand break repair protein) The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Rad50, a protein involved in DNA double-strand break repair. This protein forms a complex with MRE11 and NBS1. The protein complex binds to DNA and displays numerous enzymatic activities that are required for nonhomologous joining of DNA ends. This protein, cooperating with its partners, is important for DNA double-strand break repair, cell cycle checkpoint activation, telomere maintenance, and meiotic recombination. Knockout studies of the mouse homolog suggest this gene is essential for cell growth and viability. Mutations in this gene are the cause of Nijmegen breakage syndrome-like disorder.[provided by RefSeq, Apr 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.9
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RAD50 | NM_005732.4 | c.3464A>C | p.Tyr1155Ser | missense_variant | 22/25 | ENST00000378823.8 | NP_005723.2 | |
TH2LCRR | NR_132124.1 | n.153+969T>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RAD50 | ENST00000378823.8 | c.3464A>C | p.Tyr1155Ser | missense_variant | 22/25 | 1 | NM_005732.4 | ENSP00000368100 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 2AN: 152124Hom.: 0 Cov.: 32 FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000343 AC: 5AN: 1458702Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 725762
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GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000131 AC: 2AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74444
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Data not reliable, filtered out with message: AS_VQSR
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;.;.;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;.;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
.;.;.;H
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
REVEL
Pathogenic
Sift4G
Uncertain
.;.;.;D
Polyphen
1.0
.;.;.;D
Vest4
0.90
MutPred
0.73
.;.;.;Gain of disorder (P = 0.0088);
MVP
0.78
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at