19-10133380-A-G
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4BP6_ModerateBS2
The NM_001130823.3(DNMT1):c.*287T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.000354 in 502,820 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 Benign (★).
Frequency
Genomes: 𝑓 0.00088 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
DNMT1
NM_001130823.3 3_prime_UTR
NM_001130823.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.69
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 -7 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.09).
BP6
?
Variant 19-10133380-A-G is Benign according to our data. Variant chr19-10133380-A-G is described in ClinVar as [Benign]. Clinvar id is 891484.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 134 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNMT1 | NM_001130823.3 | c.*287T>C | 3_prime_UTR_variant | 41/41 | ENST00000359526.9 | ||
DNMT1 | NM_001318730.2 | c.*287T>C | 3_prime_UTR_variant | 40/40 | |||
DNMT1 | NM_001318731.2 | c.*287T>C | 3_prime_UTR_variant | 41/41 | |||
DNMT1 | NM_001379.4 | c.*287T>C | 3_prime_UTR_variant | 40/40 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNMT1 | ENST00000359526.9 | c.*287T>C | 3_prime_UTR_variant | 41/41 | 1 | NM_001130823.3 |
Frequencies
GnomAD3 genomes ? AF: 0.000880 AC: 134AN: 152250Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.000126 AC: 44AN: 350452Hom.: 0 Cov.: 2 AF XY: 0.0000874 AC XY: 16AN XY: 183158
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GnomAD4 genome ? AF: 0.000879 AC: 134AN: 152368Hom.: 0 Cov.: 32 AF XY: 0.000939 AC XY: 70AN XY: 74510
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary sensory neuropathy-deafness-dementia syndrome Benign:1
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. - |
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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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at