rs1223065154
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PP2PP3_ModerateBP6_Moderate
The NM_001130823.3(DNMT1):c.2377G>T(p.Ala793Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000062 in 1,614,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
DNMT1
NM_001130823.3 missense
NM_001130823.3 missense
Scores
5
10
4
Clinical Significance
Conservation
PhyloP100: 5.97
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 Uncertain_significance. Variant got 1 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, DNMT1
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.884
BP6
?
Variant 19-10149857-C-A is Benign according to our data. Variant chr19-10149857-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 472266.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNMT1 | NM_001130823.3 | c.2377G>T | p.Ala793Ser | missense_variant | 25/41 | ENST00000359526.9 | |
DNMT1 | NM_001318730.2 | c.2329G>T | p.Ala777Ser | missense_variant | 24/40 | ||
DNMT1 | NM_001379.4 | c.2329G>T | p.Ala777Ser | missense_variant | 24/40 | ||
DNMT1 | NM_001318731.2 | c.2014G>T | p.Ala672Ser | missense_variant | 25/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNMT1 | ENST00000359526.9 | c.2377G>T | p.Ala793Ser | missense_variant | 25/41 | 1 | NM_001130823.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152210Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461870Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727228
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74356
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary sensory neuropathy-deafness-dementia syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Pathogenic
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;D
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MutPred
Gain of disorder (P = 0.0344);.;
MVP
MPC
2.1
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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