rs16999593
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBA1
The NM_001130823.3(DNMT1):āc.290A>Gā(p.His97Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00824 in 1,614,168 control chromosomes in the GnomAD database, including 1,034 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H97Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_001130823.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNMT1 | NM_001130823.3 | c.290A>G | p.His97Arg | missense_variant | 4/41 | ENST00000359526.9 | |
DNMT1 | NM_001318730.2 | c.290A>G | p.His97Arg | missense_variant | 4/40 | ||
DNMT1 | NM_001379.4 | c.290A>G | p.His97Arg | missense_variant | 4/40 | ||
DNMT1 | NM_001318731.2 | c.-74A>G | 5_prime_UTR_variant | 4/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNMT1 | ENST00000359526.9 | c.290A>G | p.His97Arg | missense_variant | 4/41 | 1 | NM_001130823.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0119 AC: 1818AN: 152156Hom.: 141 Cov.: 31
GnomAD3 exomes AF: 0.0245 AC: 6155AN: 251494Hom.: 509 AF XY: 0.0211 AC XY: 2872AN XY: 135922
GnomAD4 exome AF: 0.00786 AC: 11484AN: 1461894Hom.: 892 Cov.: 31 AF XY: 0.00755 AC XY: 5490AN XY: 727248
GnomAD4 genome ? AF: 0.0120 AC: 1822AN: 152274Hom.: 142 Cov.: 31 AF XY: 0.0130 AC XY: 966AN XY: 74450
ClinVar
Submissions by phenotype
not provided Benign:4
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Aug 30, 2018 | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 14, 2015 | - - |
Hereditary sensory neuropathy-deafness-dementia syndrome Benign:2
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. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at