ClinVar Miner

Submissions for variant NM_024782.3(NHEJ1):c.743G>C (p.Gly248Ala)

gnomAD frequency: 0.00002  dbSNP: rs199723096
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001880556 SCV002120312 uncertain significance Cernunnos-XLF deficiency 2021-04-27 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with NHEJ1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with alanine at codon 248 of the NHEJ1 protein (p.Gly248Ala). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and alanine.
Ambry Genetics RCV002547941 SCV003626659 uncertain significance Inborn genetic diseases 2022-06-17 criteria provided, single submitter clinical testing The c.743G>C (p.G248A) alteration is located in exon 7 (coding exon 6) of the NHEJ1 gene. This alteration results from a G to C substitution at nucleotide position 743, causing the glycine (G) at amino acid position 248 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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