5-69400113-T-G
Variant names:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_133338.3(RAD17):āc.1637T>Gā(p.Leu546Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,597,920 control chromosomes in the GnomAD database, including 77,290 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: š 0.25 ( 5668 hom., cov: 31)
Exomes š: 0.31 ( 71622 hom. )
Consequence
RAD17
NM_133338.3 missense
NM_133338.3 missense
Scores
6
5
7
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 7.45
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 Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0021357536).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.251 AC: 38000AN: 151598Hom.: 5664 Cov.: 31
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GnomAD3 exomes AF: 0.292 AC: 71463AN: 244966Hom.: 11118 AF XY: 0.300 AC XY: 39861AN XY: 132696
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GnomAD4 exome AF: 0.310 AC: 448794AN: 1446206Hom.: 71622 Cov.: 33 AF XY: 0.312 AC XY: 224674AN XY: 719190
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GnomAD4 genome AF: 0.250 AC: 38004AN: 151714Hom.: 5668 Cov.: 31 AF XY: 0.254 AC XY: 18848AN XY: 74142
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1162
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1288
ESP6500AA
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370
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2767
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36329
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1143
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3474
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;.;.;.;.;.;.;.;.;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
.;.;.;.;.;.;T;.;T;T;T;T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;.;.;.;.;.;.;.;.;M;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D;D;.;D;D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D;D;D;.;D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D
Polyphen
D;D;D;.;D;D;D;D;D;.;D;.
Vest4
MPC
0.42
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