NM_001130823.3:c.1281T>C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_001130823.3(DNMT1):c.1281T>C(p.Ser427Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001130823.3 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNMT1 | NM_001130823.3 | c.1281T>C | p.Ser427Ser | splice_region_variant, synonymous_variant | Exon 18 of 41 | ENST00000359526.9 | NP_001124295.1 | |
DNMT1 | NM_001318730.2 | c.1233T>C | p.Ser411Ser | splice_region_variant, synonymous_variant | Exon 17 of 40 | NP_001305659.1 | ||
DNMT1 | NM_001379.4 | c.1233T>C | p.Ser411Ser | splice_region_variant, synonymous_variant | Exon 17 of 40 | NP_001370.1 | ||
DNMT1 | NM_001318731.2 | c.918T>C | p.Ser306Ser | splice_region_variant, synonymous_variant | Exon 18 of 41 | NP_001305660.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary sensory neuropathy-deafness-dementia syndrome Uncertain:1
This sequence change affects codon 427 of the DNMT1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the DNMT1 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DNMT1-related disease. ClinVar contains an entry for this variant (Variation ID: 539623). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at