ClinVar Miner

Submissions for variant NM_001130823.3(DNMT1):c.3394+4C>T

gnomAD frequency: 0.00002  dbSNP: rs781376510
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001065728 SCV001230701 uncertain significance Hereditary sensory neuropathy-deafness-dementia syndrome 2024-01-11 criteria provided, single submitter clinical testing This sequence change falls in intron 31 of the DNMT1 gene. It does not directly change the encoded amino acid sequence of the DNMT1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs781376510, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with DNMT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 859581). 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 is not likely to affect RNA splicing. 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.
Fulgent Genetics, Fulgent Genetics RCV002489692 SCV002775835 uncertain significance Autosomal dominant cerebellar ataxia, deafness and narcolepsy; Hereditary sensory neuropathy-deafness-dementia syndrome 2021-10-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002555846 SCV003654807 uncertain significance Inborn genetic diseases 2023-11-30 criteria provided, single submitter clinical testing The c.3346+4C>T intronic alteration results from a C to T substitution 4 nucleotides after coding exon 30 of the DNMT1 gene. Based on data from gnomAD, the T allele has an overall frequency of 0.003% (8/251334) total alleles studied. The highest observed frequency was 0.016% (1/6138) of Other alleles. This nucleotide position is poorly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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