rs1554774708
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM2PP2PP3_StrongPP5_Moderate
The NM_004408.4(DNM1):c.1190G>A(p.Gly397Asp) 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 Pathogenic (★).
Frequency
Consequence
NM_004408.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNM1 | ENST00000372923.8 | c.1190G>A | p.Gly397Asp | missense_variant | Exon 9 of 22 | 1 | NM_004408.4 | ENSP00000362014.4 | ||
DNM1 | ENST00000634267.2 | c.1190G>A | p.Gly397Asp | missense_variant | Exon 9 of 22 | 5 | ENSP00000489096.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
The c.1190G>A (p.G397D) alteration is located in exon 9 (coding exon 9) of the DNM1 gene. This alteration results from a G to A substitution at nucleotide position 1190, causing the glycine (G) at amino acid position 397 to be replaced by an aspartic acid (D). The alteration is not observed in healthy cohorts:_x000D_ Based on data from the NHLBI Exome Sequencing Project (ESP), the DNM1 c.1190G>A alteration was not observed among 5,837 individuals tested. Allele frequency data for this nucleotide position are not currently available from the 1000 Genomes Project, and the alteration is not currently listed in the Database of Single Nucleotide Polymorphisms (dbSNP)._x000D_ Though some variants may appear to be rare due to database-specific ethnic underrepresentation, rare missense alleles commonly exhibit a deleterious effect on protein function (Kryukov, 2007; Tennessen, 2012). IF USED, PULL THESE INTO REFERENCES:_x000D_ Kryukov GV, et al. (2007) Am J Hum Genet 80:727-739. Tennessen JA, et al. (2012) Science 337(64):64-69. The altered nucleotide is conserved throughout evolution:_x000D_ The c.1190G nucleotide is completely conserved in available vertebrate species._x000D_ _x000D_ The altered amino acid is conserved throughout evolution:_x000D_ The p.G397 amino acid is completely conserved in available vertebrate species. The c.1190G>A (p.G397D) alteration is located in coding exon 9 of the DNM1 gene. This alteration results from a G to A substitution at nucleotide position 1190, resulting in an amino acid substitution of aspartic acid (D) for glycine (G) at codon 397. The alteration is predicted deleterious by in silico models:_x000D_ The p.G397D alteration is predicted to be probably damaging by Polyphen and deleterious by SIFT in silico analyses._x000D_ _x000D_ The alteration is predicted not to affect splicing by in silico models:_x000D_ Based on BDGP and ESEfinder splice site in silico tools, this alteration does not have any significant effect on the native acceptor/donor splice site; however, direct evidence is unavailable. Based on the available evidence, this alteration is classified as pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at