rs199473691
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PS1PM1PM2PP2PP3PP5
The NM_001130823.3(DNMT1):c.1518_1520delinsATA(p.Asp506_Pro507delinsGluTyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Pathogenicin Lovd.
Frequency
Genomes: not found (cov: 32)
Consequence
DNMT1
NM_001130823.3 missense
NM_001130823.3 missense
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.97
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 Pathogenic. Variant got 11 ACMG points.
PS1
?
Transcript NM_001130823.3 (DNMT1) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in Lovd
PM1
?
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 1 benign, 3 uncertain in NM_001130823.3
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, DNMT1
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
PP5
?
Variant 19-10155029-GGA-TAT is Pathogenic according to our data. Variant chr19-10155029-GGA-TAT is described in ClinVar as [Pathogenic]. Clinvar id is 29683.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNMT1 | NM_001130823.3 | c.1518_1520delinsATA | p.Asp506_Pro507delinsGluTyr | missense_variant | 20/41 | ENST00000359526.9 | |
DNMT1 | NM_001318730.2 | c.1470_1472delinsATA | p.Asp490_Pro491delinsGluTyr | missense_variant | 19/40 | ||
DNMT1 | NM_001318731.2 | c.1155_1157delinsATA | p.Asp385_Pro386delinsGluTyr | missense_variant | 20/41 | ||
DNMT1 | NM_001379.4 | c.1470_1472delinsATA | p.Asp490_Pro491delinsGluTyr | missense_variant | 19/40 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNMT1 | ENST00000359526.9 | c.1518_1520delinsATA | p.Asp506_Pro507delinsGluTyr | missense_variant | 20/41 | 1 | NM_001130823.3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hereditary sensory neuropathy-deafness-dementia syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2011 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at