rs1554767317
Variant summary
Our verdict is Pathogenic. Variant got 17 ACMG points: 17P and 0B. PM1PM2PP2PP3_StrongPP5_Very_Strong
The NM_004408.4(DNM1):c.134G>A(p.Ser45Asn) 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. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_004408.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 17 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNM1 | ENST00000372923.8 | c.134G>A | p.Ser45Asn | missense_variant | Exon 1 of 22 | 1 | NM_004408.4 | ENSP00000362014.4 | ||
DNM1 | ENST00000634267.2 | c.134G>A | p.Ser45Asn | missense_variant | Exon 1 of 22 | 5 | ENSP00000489096.1 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1395346Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 694148
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Developmental and epileptic encephalopathy, 31A Pathogenic:1
This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with DNM1-related encephalopathy (PMID: 28667181). ClinVar contains an entry for this variant (Variation ID: 520840). TThis variant has been reported to affect DNM1 protein function, also known as Dyn1 (PMID: 11553700, 19084268, 29668686). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This sequence change replaces serine with asparagine at codon 45 of the DNM1 protein (p.Ser45Asn). The serine residue is highly conserved and there is a small physicochemical difference between serine and asparagine. -
Inborn genetic diseases Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at