rs765347113
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The ENST00000359526.9(DNMT1):āc.4427A>Gā(p.His1476Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000683 in 1,610,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. H1476Q) has been classified as Likely benign.
Frequency
Consequence
ENST00000359526.9 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNMT1 | NM_001130823.3 | c.4427A>G | p.His1476Arg | missense_variant | 37/41 | ENST00000359526.9 | NP_001124295.1 | |
DNMT1 | NM_001318730.2 | c.4379A>G | p.His1460Arg | missense_variant | 36/40 | NP_001305659.1 | ||
DNMT1 | NM_001379.4 | c.4379A>G | p.His1460Arg | missense_variant | 36/40 | NP_001370.1 | ||
DNMT1 | NM_001318731.2 | c.4064A>G | p.His1355Arg | missense_variant | 37/41 | NP_001305660.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNMT1 | ENST00000359526.9 | c.4427A>G | p.His1476Arg | missense_variant | 37/41 | 1 | NM_001130823.3 | ENSP00000352516 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000331 AC: 8AN: 241432Hom.: 0 AF XY: 0.0000152 AC XY: 2AN XY: 131228
GnomAD4 exome AF: 0.00000686 AC: 10AN: 1458474Hom.: 0 Cov.: 32 AF XY: 0.00000414 AC XY: 3AN XY: 725290
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74362
ClinVar
Submissions by phenotype
Hereditary sensory neuropathy-deafness-dementia syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 31, 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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 present in population databases (rs765347113, ExAC 0.07%). This sequence change replaces histidine with arginine at codon 1476 of the DNMT1 protein (p.His1476Arg). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and arginine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at