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GeneBe

rs980964237

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005732.4(RAD50):c.1723C>A(p.Gln575Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q575H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

RAD50
NM_005732.4 missense

Scores

5
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.81
Variant links:
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32247487).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RAD50NM_005732.4 linkuse as main transcriptc.1723C>A p.Gln575Lys missense_variant 11/25 ENST00000378823.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RAD50ENST00000378823.8 linkuse as main transcriptc.1723C>A p.Gln575Lys missense_variant 11/251 NM_005732.4 P1Q92878-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.095
T
BayesDel_noAF
Benign
-0.37
Cadd
Benign
22
Dann
Uncertain
0.99
Eigen
Uncertain
0.48
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Uncertain
0.97
D
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.32
T;T;T;T;T
MetaSVM
Benign
-0.61
T
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.62
T
Polyphen
0.21
.;.;.;B;.
Vest4
0.61
MutPred
0.34
.;.;.;Gain of methylation at Q575 (P = 0.0115);.;
MVP
0.50
ClinPred
0.92
D
GERP RS
6.1
Varity_R
0.20
gMVP
0.67

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-131927656; API