rs1255037718
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001130823.3(DNMT1):c.4327C>A(p.His1443Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,609,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001130823.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNMT1 | NM_001130823.3 | c.4327C>A | p.His1443Asn | missense_variant | 37/41 | ENST00000359526.9 | |
DNMT1 | NM_001318730.2 | c.4279C>A | p.His1427Asn | missense_variant | 36/40 | ||
DNMT1 | NM_001379.4 | c.4279C>A | p.His1427Asn | missense_variant | 36/40 | ||
DNMT1 | NM_001318731.2 | c.3964C>A | p.His1322Asn | missense_variant | 37/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNMT1 | ENST00000359526.9 | c.4327C>A | p.His1443Asn | missense_variant | 37/41 | 1 | NM_001130823.3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152244Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000413 AC: 1AN: 242216Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 131790
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1457582Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 724940
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152244Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74392
ClinVar
Submissions by phenotype
Hereditary sensory neuropathy-deafness-dementia syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 24, 2017 | 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 asparagine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with DNMT1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with asparagine at codon 1443 of the DNMT1 protein (p.His1443Asn). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and asparagine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at