ClinVar Miner

Submissions for variant NM_133433.4(NIPBL):c.1229T>C (p.Ile410Thr)

dbSNP: rs546539357
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
New York Genome Center RCV002275557 SCV002564153 uncertain significance Cornelia de Lange syndrome 1 2021-09-08 criteria provided, single submitter clinical testing The c.1229T>C (p.Ile410Thr) variant identified in the NIPBL gene substitutes an Isoleucine for Threonine at amino acid 410/2805 (exon 9/47). This amino acid is not very well conserved, and many mammalian species have a Valine at this position. This variant is found with low frequency in gnomAD(v2.1.1)(1 heterozygote, 0 homozygotes; allele frequency:4.0e-6) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms predict this variant to be Damaging (SIFT; score:0.002) and Benign (REVEL; score:0.287) to the function of the canonical transcript. While this variant(c.1229T>C, p.Ile410Thr) is absent from ClinVar, a different nucleotide change at the same amino acid (c.1228A>G, p.Ile410Val) is reported as a Variant of Uncertain Significance (VarID:904960). To our current knowledge, the p.Ile410Thr variant identified here has not been previously reported in affected individuals in theliterature. The p.Ile410 residue is not within a mapped domain of NIPBL (UniProkKB:Q6KC79). Given the lack of compelling evidence for its pathogenicity, the c.1229T>C (p.Ile410Thr) variant identified in the NIPBL gene is reported as a Variant of Uncertain Significance.

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