rs979325432
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 3P and 8B. PM2PP2BP4_StrongBS2
The NM_001130823.3(DNMT1):āc.1393C>Gā(p.Leu465Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,456,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L465P) has been classified as Uncertain significance.
Frequency
Consequence
NM_001130823.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNMT1 | NM_001130823.3 | c.1393C>G | p.Leu465Val | missense_variant | 18/41 | ENST00000359526.9 | |
DNMT1 | NM_001318730.2 | c.1345C>G | p.Leu449Val | missense_variant | 17/40 | ||
DNMT1 | NM_001379.4 | c.1345C>G | p.Leu449Val | missense_variant | 17/40 | ||
DNMT1 | NM_001318731.2 | c.1030C>G | p.Leu344Val | missense_variant | 18/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNMT1 | ENST00000359526.9 | c.1393C>G | p.Leu465Val | missense_variant | 18/41 | 1 | NM_001130823.3 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1456820Hom.: 0 Cov.: 27 AF XY: 0.00000138 AC XY: 1AN XY: 725036
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Hereditary sensory neuropathy-deafness-dementia syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2022 | 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 valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 577611). 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 leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 465 of the DNMT1 protein (p.Leu465Val). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at