rs1555690467
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate
The NM_001130823.3(DNMT1):c.2474C>T(p.Ser825Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S825S) has been classified as Likely benign.
Frequency
Consequence
NM_001130823.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNMT1 | NM_001130823.3 | c.2474C>T | p.Ser825Leu | missense_variant | 26/41 | ENST00000359526.9 | |
DNMT1 | NM_001318730.2 | c.2426C>T | p.Ser809Leu | missense_variant | 25/40 | ||
DNMT1 | NM_001379.4 | c.2426C>T | p.Ser809Leu | missense_variant | 25/40 | ||
DNMT1 | NM_001318731.2 | c.2111C>T | p.Ser704Leu | missense_variant | 26/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNMT1 | ENST00000359526.9 | c.2474C>T | p.Ser825Leu | missense_variant | 26/41 | 1 | NM_001130823.3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary sensory neuropathy-deafness-dementia syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 20, 2022 | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 539609). This variant has not been reported in the literature in individuals affected with DNMT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 825 of the DNMT1 protein (p.Ser825Leu). 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