rs921235584

Variant summary

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

The NM_002485.5(NBN):​c.1922A>T​(p.Asp641Val) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D641G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

NBN
NM_002485.5 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.40
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=0.15487236).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NBNNM_002485.5 linkuse as main transcriptc.1922A>T p.Asp641Val missense_variant 13/16 ENST00000265433.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NBNENST00000265433.8 linkuse as main transcriptc.1922A>T p.Asp641Val missense_variant 13/161 NM_002485.5 P1

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
0.094
BayesDel_addAF
Benign
-0.090
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
19
DANN
Benign
0.78
DEOGEN2
Benign
0.38
T;T
Eigen
Benign
-0.25
Eigen_PC
Benign
-0.29
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.79
T;T
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.9
L;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.29
T
PROVEAN
Uncertain
-2.9
D;D
REVEL
Benign
0.054
Sift
Uncertain
0.0050
D;D
Sift4G
Benign
0.30
T;T
Polyphen
0.89
P;.
Vest4
0.22
MutPred
0.23
Gain of loop (P = 3e-04);.;
MVP
0.77
MPC
0.18
ClinPred
0.71
D
GERP RS
4.5
Varity_R
0.13
gMVP
0.27

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.11
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: chr8-90958516; API