rs587781557
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_002485.5(NBN):c.1480C>A(p.Gln494Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,036 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Q494P) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NBN | NM_002485.5 | c.1480C>A | p.Gln494Lys | missense_variant | 11/16 | ENST00000265433.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NBN | ENST00000265433.8 | c.1480C>A | p.Gln494Lys | missense_variant | 11/16 | 1 | NM_002485.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152036Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152036Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74266
ClinVar
Submissions by phenotype
Microcephaly, normal intelligence and immunodeficiency Uncertain:3
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 16, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 07, 2022 | This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 494 of the NBN protein (p.Gln494Lys). 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: 141181). 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. - |
Aplastic anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 12, 2024 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 25, 2023 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 04, 2024 | The p.Q494K variant (also known as c.1480C>A), located in coding exon 11 of the NBN gene, results from a C to A substitution at nucleotide position 1480. The glutamine at codon 494 is replaced by lysine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species.. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at