rs587781980

Variant names:

• chr5-132579971-T-A
• NM_005732.4:c.661T>A

Your query was ambiguous. Multiple possible variants found:

• chr5-132579971-T-A
• chr5-132579971-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005732.4(RAD50):​c.661T>A​(p.Cys221Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,460,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000041 (0 hom.)
• Consequence: RAD50 NM_005732.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.65

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]

ENSG00000283782 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12210384).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD50	NM_005732.4	c.661T>A	p.Cys221Ser	missense_variant	Exon 5 of 25	ENST00000378823.8	NP_005723.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD50	ENST00000378823.8	c.661T>A	p.Cys221Ser	missense_variant	Exon 5 of 25	1	NM_005732.4	ENSP00000368100.4
ENSG00000283782	ENST00000640655.2	c.364T>A	p.Cys122Ser	missense_variant	Exon 6 of 26	5		ENSP00000491596.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460470 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 726630

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

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	0.089
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Benign	0.81
DEOGEN2	Benign	0.035	.;.;.;T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.050
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.73	.;.;T;T;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.34	.;.;.;N;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.54	.;.;.;.;N
REVEL	Benign	0.061
Sift	Benign	0.74	.;.;.;.;T
Sift4G	Benign	0.85	.;.;.;T;T
Polyphen		0.018	.;.;.;B;.
Vest4		0.38
MutPred		0.30		.;.;.;Gain of phosphorylation at C221 (P = 0.0178);Gain of phosphorylation at C221 (P = 0.0178);
MVP		0.43
ClinPred		0.73	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.093
gMVP		0.14

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: chr5-131915663;