rs781671474
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_002485.5(NBN):c.371G>A(p.Gly124Glu) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G124R) has been classified as Uncertain significance.
Frequency
Consequence
NM_002485.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NBN | NM_002485.5 | c.371G>A | p.Gly124Glu | missense_variant | 4/16 | ENST00000265433.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NBN | ENST00000265433.8 | c.371G>A | p.Gly124Glu | missense_variant | 4/16 | 1 | NM_002485.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251154Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135744
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Microcephaly, normal intelligence and immunodeficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 13, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 124 of the NBN protein (p.Gly124Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NBN-related conditions. ClinVar contains an entry for this variant (Variation ID: 239198). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at