5-132609198-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005732.4(RAD50):​c.2911G>T​(p.Asp971Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

RAD50
NM_005732.4 missense

Scores

4
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.38
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13359231).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAD50NM_005732.4 linkc.2911G>T p.Asp971Tyr missense_variant Exon 18 of 25 ENST00000378823.8 NP_005723.2 Q92878-1A5D6Y3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAD50ENST00000378823.8 linkc.2911G>T p.Asp971Tyr missense_variant Exon 18 of 25 1 NM_005732.4 ENSP00000368100.4 Q92878-1
ENSG00000283782ENST00000640655.2 linkc.2614G>T p.Asp872Tyr missense_variant Exon 19 of 26 5 ENSP00000491596.2 A0A1W2PQ90

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1458956
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
725606
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.074
T
BayesDel_noAF
Benign
-0.34
CADD
Uncertain
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.21
.;.;.;T
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.13
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.93
.;.;D;D
M_CAP
Benign
0.0049
T
MetaRNN
Benign
0.13
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
.;.;.;L
PrimateAI
Benign
0.46
T
REVEL
Benign
0.063
Sift4G
Uncertain
0.032
.;.;.;D
Polyphen
0.58
.;.;.;P
Vest4
0.57
MutPred
0.41
.;.;.;Loss of ubiquitination at K973 (P = 0.0524);
MVP
0.57
ClinPred
0.84
D
GERP RS
2.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.059
gMVP
0.42

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: chr5-131944890; API