chr5-69400053-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_133338.3(RAD17):c.1577G>A(p.Arg526Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000127 in 1,578,352 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000034 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
RAD17
NM_133338.3 missense
NM_133338.3 missense
Scores
1
15
Clinical Significance
Conservation
PhyloP100: 5.06
Genes affected
RAD17 (HGNC:9807): (RAD17 checkpoint clamp loader component) The protein encoded by this gene is highly similar to the gene product of Schizosaccharomyces pombe rad17, a cell cycle checkpoint gene required for cell cycle arrest and DNA damage repair in response to DNA damage. This protein shares strong similarity with DNA replication factor C (RFC), and can form a complex with RFCs. This protein binds to chromatin prior to DNA damage and is phosphorylated by the checkpoint kinase ATR following damage. This protein recruits the RAD1-RAD9-HUS1 checkpoint protein complex onto chromatin after DNA damage, which may be required for its phosphorylation. The phosphorylation of this protein is required for the DNA-damage-induced cell cycle G2 arrest, and is thought to be a critical early event during checkpoint signaling in DNA-damaged cells. Multiple alternatively spliced transcript variants of this gene, which encode four distinct protein isoforms, have been reported. Two pseudogenes, located on chromosomes 7 and 13, have been identified. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.22809738).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAD17 | NM_133338.3 | c.1577G>A | p.Arg526Gln | missense_variant | 17/19 | ENST00000354868.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD17 | ENST00000354868.10 | c.1577G>A | p.Arg526Gln | missense_variant | 17/19 | 1 | NM_133338.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000335 AC: 5AN: 149066Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000169 AC: 4AN: 237034Hom.: 0 AF XY: 0.0000156 AC XY: 2AN XY: 128542
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GnomAD4 exome AF: 0.0000105 AC: 15AN: 1429286Hom.: 0 Cov.: 30 AF XY: 0.0000112 AC XY: 8AN XY: 711242
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GnomAD4 genome ? AF: 0.0000335 AC: 5AN: 149066Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 72446
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 15, 2023 | The c.1610G>A (p.R537Q) alteration is located in exon 14 (coding exon 14) of the RAD17 gene. This alteration results from a G to A substitution at nucleotide position 1610, causing the arginine (R) at amino acid position 537 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N;.;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T;.;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
P;P;P;.;P;P;P;P;P;.;P;.
Vest4
MutPred
0.76
.;Gain of helix (P = 0.0199);.;.;.;.;.;.;.;.;Gain of helix (P = 0.0199);.;
MVP
MPC
0.074
ClinPred
T
GERP RS
Varity_R
gMVP
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