rs766504703
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2
The NM_001130823.3(DNMT1):āc.857T>Cā(p.Val286Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V286M) has been classified as Likely benign.
Frequency
Consequence
NM_001130823.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNMT1 | NM_001130823.3 | c.857T>C | p.Val286Ala | missense_variant | 11/41 | ENST00000359526.9 | |
DNMT1 | NM_001318730.2 | c.809T>C | p.Val270Ala | missense_variant | 10/40 | ||
DNMT1 | NM_001379.4 | c.809T>C | p.Val270Ala | missense_variant | 10/40 | ||
DNMT1 | NM_001318731.2 | c.494T>C | p.Val165Ala | missense_variant | 11/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNMT1 | ENST00000359526.9 | c.857T>C | p.Val286Ala | missense_variant | 11/41 | 1 | NM_001130823.3 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152136Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251492Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135922
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461872Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727232
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152136Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74304
ClinVar
Submissions by phenotype
Hereditary sensory neuropathy-deafness-dementia syndrome;C3807295:Autosomal dominant cerebellar ataxia, deafness and narcolepsy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 21, 2021 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 05, 2022 | The p.V270A variant (also known as c.809T>C), located in coding exon 10 of the DNMT1 gene, results from a T to C substitution at nucleotide position 809. The valine at codon 270 is replaced by alanine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Hereditary sensory neuropathy-deafness-dementia syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 23, 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. This variant has not been reported in the literature in individuals affected with DNMT1-related conditions. This variant is present in population databases (rs766504703, gnomAD 0.004%). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 286 of the DNMT1 protein (p.Val286Ala). ClinVar contains an entry for this variant (Variation ID: 573027). 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 alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 14, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at