rs369470867
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.Pro129Pro) 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
Consequence
NM_001130823.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNMT1 | NM_001130823.3 | c.387C>T | p.Pro129Pro | synonymous_variant | Exon 4 of 41 | ENST00000359526.9 | NP_001124295.1 | |
DNMT1 | NM_001318730.2 | c.387C>T | p.Pro129Pro | synonymous_variant | Exon 4 of 40 | NP_001305659.1 | ||
DNMT1 | NM_001379.4 | c.387C>T | p.Pro129Pro | synonymous_variant | Exon 4 of 40 | NP_001370.1 | ||
DNMT1 | NM_001318731.2 | c.24C>T | p.Pro8Pro | synonymous_variant | Exon 4 of 41 | NP_001305660.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000921 AC: 14AN: 152054Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000131 AC: 33AN: 251174Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135814
GnomAD4 exome AF: 0.000114 AC: 167AN: 1461692Hom.: 0 Cov.: 31 AF XY: 0.000124 AC XY: 90AN XY: 727166
GnomAD4 genome AF: 0.0000920 AC: 14AN: 152172Hom.: 0 Cov.: 31 AF XY: 0.0000807 AC XY: 6AN XY: 74390
ClinVar
Submissions by phenotype
Hereditary sensory neuropathy-deafness-dementia syndrome Benign:2
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. -
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not provided Benign:2
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DNMT1: BP4, BP7 -
not specified Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at