rs371779379
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001130823.3(DNMT1):c.3806+6C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,607,566 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 1 hom. )
Consequence
DNMT1
NM_001130823.3 splice_donor_region, intron
NM_001130823.3 splice_donor_region, intron
Scores
2
Splicing: ADA: 0.00001692
2
Clinical Significance
Conservation
PhyloP100: -1.01
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 -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
?
Variant 19-10140040-G-A is Benign according to our data. Variant chr19-10140040-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 289710.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1, Benign=1}.
BS2
?
High AC in GnomAd at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNMT1 | NM_001130823.3 | c.3806+6C>T | splice_donor_region_variant, intron_variant | ENST00000359526.9 | |||
DNMT1 | NM_001318730.2 | c.3758+6C>T | splice_donor_region_variant, intron_variant | ||||
DNMT1 | NM_001318731.2 | c.3443+6C>T | splice_donor_region_variant, intron_variant | ||||
DNMT1 | NM_001379.4 | c.3758+6C>T | splice_donor_region_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNMT1 | ENST00000359526.9 | c.3806+6C>T | splice_donor_region_variant, intron_variant | 1 | NM_001130823.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152242Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000398 AC: 97AN: 243994Hom.: 2 AF XY: 0.000415 AC XY: 55AN XY: 132592
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GnomAD4 exome AF: 0.000127 AC: 185AN: 1455206Hom.: 1 Cov.: 33 AF XY: 0.000148 AC XY: 107AN XY: 724274
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 08, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 11, 2016 | - - |
Hereditary sensory neuropathy-deafness-dementia syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at