rs587777862
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Moderate
The NM_004408.4(DNM1):c.1076G>C(p.Gly359Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/20 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G359R) has been classified as Pathogenic.
Frequency
Consequence
NM_004408.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNM1 | NM_004408.4 | c.1076G>C | p.Gly359Ala | missense_variant | 8/22 | ENST00000372923.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNM1 | ENST00000372923.8 | c.1076G>C | p.Gly359Ala | missense_variant | 8/22 | 1 | NM_004408.4 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 33
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 31 Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | DASA | Feb 05, 2022 | The c.1076G>C;p.(Gly359Ala) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 156559; OMIM: 602377.0003; PMID: 25262651) - PS4_supporting. Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product (PMID: 27066543) - PS3_supporting. The variant is located in a mutational hot spot and/or critical and well-established functional domain (Dynamin) - PM1. This variant is not present in population databases (rs587777862; gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. Pathogenic missense variant in this residue have been reported (ClinVar ID: 520737 - c.1075G>A;p.(Gly359Arg)) - PM5. The variant was assumed de novo; but without confirmation of paternity and maternity (PMID: 25262651) - PM6. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is likely pathogenic. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 02, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at