rs202058239
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001130823.3(DNMT1):c.1896G>A(p.Thr632=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 1,614,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00018 ( 0 hom. )
Consequence
DNMT1
NM_001130823.3 synonymous
NM_001130823.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.68
Genes affected
DNMT1 (HGNC:2976): (DNA methyltransferase 1) This gene encodes an enzyme that transfers methyl groups to cytosine nucleotides of genomic DNA. This protein is the major enzyme responsible for maintaining methylation patterns following DNA replication and shows a preference for hemi-methylated DNA. Methylation of DNA is an important component of mammalian epigenetic gene regulation. Aberrant methylation patterns are found in human tumors and associated with developmental abnormalities. Variation in this gene has been associated with cerebellar ataxia, deafness, and narcolepsy, and neuropathy, hereditary sensory, type IE. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
Variant 19-10154416-C-T is Benign according to our data. Variant chr19-10154416-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 384833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.68 with no splicing effect.
BS2
?
High AC in GnomAd4 at 23 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNMT1 | NM_001130823.3 | c.1896G>A | p.Thr632= | synonymous_variant | 22/41 | ENST00000359526.9 | |
DNMT1 | NM_001318730.2 | c.1848G>A | p.Thr616= | synonymous_variant | 21/40 | ||
DNMT1 | NM_001379.4 | c.1848G>A | p.Thr616= | synonymous_variant | 21/40 | ||
DNMT1 | NM_001318731.2 | c.1533G>A | p.Thr511= | synonymous_variant | 22/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNMT1 | ENST00000359526.9 | c.1896G>A | p.Thr632= | synonymous_variant | 22/41 | 1 | NM_001130823.3 |
Frequencies
GnomAD3 genomes ? AF: 0.000151 AC: 23AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000262 AC: 66AN: 251446Hom.: 0 AF XY: 0.000287 AC XY: 39AN XY: 135898
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GnomAD4 exome AF: 0.000179 AC: 261AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.000183 AC XY: 133AN XY: 727248
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GnomAD4 genome ? AF: 0.000151 AC: 23AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74348
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary sensory neuropathy-deafness-dementia syndrome Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2024 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | DNMT1: BP4, BP7 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 10, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at