rs769485700
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_004408.4(DNM1):c.1399C>T(p.Arg467Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000127 in 1,569,408 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. R467R) has been classified as Likely benign.
Frequency
Consequence
NM_004408.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNM1 | NM_004408.4 | c.1399C>T | p.Arg467Cys | missense_variant | 11/22 | ENST00000372923.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNM1 | ENST00000372923.8 | c.1399C>T | p.Arg467Cys | missense_variant | 11/22 | 1 | NM_004408.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152178Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000120 AC: 17AN: 1417112Hom.: 0 Cov.: 30 AF XY: 0.0000114 AC XY: 8AN XY: 701102
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152296Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74462
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 31 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2022 | ClinVar contains an entry for this variant (Variation ID: 521971). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with DNM1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 467 of the DNM1 protein (p.Arg467Cys). - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 10, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at