12-32713327-C-A
Position:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP2PP3_StrongPP5
The NM_001278464.2(DNM1L):c.614C>A(p.Ala205Glu) 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 Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
DNM1L
NM_001278464.2 missense
NM_001278464.2 missense
Scores
14
3
1
Clinical Significance
Conservation
PhyloP100: 7.64
Genes affected
DNM1L (HGNC:2973): (dynamin 1 like) This gene encodes a member of the dynamin superfamily of GTPases. The encoded protein mediates mitochondrial and peroxisomal division, and is involved in developmentally regulated apoptosis and programmed necrosis. Dysfunction of this gene is implicated in several neurological disorders, including Alzheimer's disease. Mutations in this gene are associated with the autosomal dominant disorder, encephalopathy, lethal, due to defective mitochondrial and peroxisomal fission (EMPF). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2013]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PM1
In a domain Dynamin-type G (size 280) in uniprot entity DNM1L_HUMAN there are 17 pathogenic changes around while only 4 benign (81%) in NM_001278464.2
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, DNM1L
PP3
MetaRNN computational evidence supports a deleterious effect, 0.951
PP5
Variant 12-32713327-C-A is Pathogenic according to our data. Variant chr12-32713327-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 446170.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNM1L | NM_001278464.2 | c.614C>A | p.Ala205Glu | missense_variant | 7/21 | ENST00000553257.6 | |
DNM1L | NM_012062.5 | c.575C>A | p.Ala192Glu | missense_variant | 6/20 | ENST00000549701.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNM1L | ENST00000553257.6 | c.614C>A | p.Ala205Glu | missense_variant | 7/21 | 2 | NM_001278464.2 | ||
DNM1L | ENST00000549701.6 | c.575C>A | p.Ala192Glu | missense_variant | 6/20 | 1 | NM_012062.5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Optic atrophy 5 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 08, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;.;M;.;M;.;M;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D;D;D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D;D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D;D;D;D;D
Polyphen
0.92
.;.;P;.;.;.;.;.;.
Vest4
MutPred
Gain of disorder (P = 0.0289);.;Gain of disorder (P = 0.0289);.;Gain of disorder (P = 0.0289);.;Gain of disorder (P = 0.0289);.;.;
MVP
MPC
2.4
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at