rs1554559177

Variant summary

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

The NM_002485.5(NBN):​c.1273A>G​(p.Arg425Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)

Consequence

NBN
NM_002485.5 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.05
Variant links:
Genes affected
NBN (HGNC:7652): (nibrin) Mutations in this gene are associated with Nijmegen breakage syndrome, an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. The encoded protein is a member of the MRE11/RAD50 double-strand break repair complex which consists of 5 proteins. This gene product is thought to be involved in DNA double-strand break repair and DNA damage-induced checkpoint activation. [provided by RefSeq, Jul 2008]

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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=0.08768293).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NBNNM_002485.5 linkuse as main transcriptc.1273A>G p.Arg425Gly missense_variant 10/16 ENST00000265433.8 NP_002476.2 O60934

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NBNENST00000265433.8 linkuse as main transcriptc.1273A>G p.Arg425Gly missense_variant 10/161 NM_002485.5 ENSP00000265433.4 O60934

Frequencies

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.068
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
16
DANN
Benign
0.92
DEOGEN2
Benign
0.13
T;T
Eigen
Benign
-0.85
Eigen_PC
Benign
-0.79
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.75
T;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.088
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N;.
PrimateAI
Benign
0.24
T
PROVEAN
Benign
-1.1
N;N
REVEL
Benign
0.052
Sift
Benign
0.12
T;T
Sift4G
Benign
0.35
T;T
Polyphen
0.0
B;.
Vest4
0.12
MutPred
0.21
Loss of MoRF binding (P = 0.0222);.;
MVP
0.61
MPC
0.085
ClinPred
0.068
T
GERP RS
4.3
Varity_R
0.19
gMVP
0.15

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr8-90967635; API