ClinVar Miner

Submissions for variant NM_002485.5(NBN):c.171G>T (p.Leu57=)

dbSNP: rs1554569001
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000571574 SCV000662707 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-05 criteria provided, single submitter clinical testing The c.171G>T variant (also known as p.L57L), located in coding exon 2 of the NBN gene. This variant results from a G to T substitution at nucleotide position 171. This nucleotide substitution does not change the leucine at codon 57. However, this change occurs in the last base pair of coding exon 2, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice donor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001835852 SCV002246898 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2022-12-12 criteria provided, single submitter clinical testing 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 480033). This variant has not been reported in the literature in individuals affected with NBN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects codon 57 of the NBN mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NBN protein. This variant also falls at the last nucleotide of exon 2, which is part of the consensus splice site for this exon.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003114686 SCV003800910 uncertain significance not specified 2023-01-06 criteria provided, single submitter clinical testing
GeneDx RCV003225090 SCV003921730 uncertain significance not provided 2023-04-26 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
Natera, Inc. RCV001835852 SCV002078684 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2020-10-22 no assertion criteria provided clinical testing

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