rs369470867
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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.387C>T(p.Pro129=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,613,864 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 0.000092 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
DNMT1
NM_001130823.3 synonymous
NM_001130823.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.354
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=-0.87).
BP6
?
Variant 19-10180408-G-A is Benign according to our data. Variant chr19-10180408-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 327926.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.354 with no splicing effect.
BS2
?
High AC in GnomAd4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNMT1 | NM_001130823.3 | c.387C>T | p.Pro129= | synonymous_variant | 4/41 | ENST00000359526.9 | |
DNMT1 | NM_001318730.2 | c.387C>T | p.Pro129= | synonymous_variant | 4/40 | ||
DNMT1 | NM_001379.4 | c.387C>T | p.Pro129= | synonymous_variant | 4/40 | ||
DNMT1 | NM_001318731.2 | c.24C>T | p.Pro8= | synonymous_variant | 4/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNMT1 | ENST00000359526.9 | c.387C>T | p.Pro129= | synonymous_variant | 4/41 | 1 | NM_001130823.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000921 AC: 14AN: 152054Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000131 AC: 33AN: 251174Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135814
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GnomAD4 exome AF: 0.000114 AC: 167AN: 1461692Hom.: 0 Cov.: 31 AF XY: 0.000124 AC XY: 90AN XY: 727166
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GnomAD4 genome ? AF: 0.0000920 AC: 14AN: 152172Hom.: 0 Cov.: 31 AF XY: 0.0000807 AC XY: 6AN XY: 74390
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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
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | DNMT1: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 19, 2020 | - - |
Computational scores
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Name
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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