rs747632184
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_002485.5(NBN):āc.1160C>Gā(p.Ser387Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,613,258 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S387S) has been classified as Likely benign.
Frequency
Consequence
NM_002485.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NBN | NM_002485.5 | c.1160C>G | p.Ser387Cys | missense_variant | 10/16 | ENST00000265433.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NBN | ENST00000265433.8 | c.1160C>G | p.Ser387Cys | missense_variant | 10/16 | 1 | NM_002485.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151952Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000679 AC: 17AN: 250354Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135388
GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461306Hom.: 1 Cov.: 33 AF XY: 0.0000509 AC XY: 37AN XY: 726964
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151952Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74204
ClinVar
Submissions by phenotype
Microcephaly, normal intelligence and immunodeficiency Uncertain:3
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 20, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 27, 2022 | This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 387 of the NBN protein (p.Ser387Cys). This variant is present in population databases (rs747632184, gnomAD 0.06%). 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: 232200). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Apr 18, 2023 | To the best of our knowledge, the variant has not been reported in the published literature. The frequency of this variant in the general population, 0.00056 (17/30580 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant. - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 31, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at