chr12-32679392-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_001278464.2(DNM1L):c.29A>G(p.Lys10Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,522 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
DNM1L
NM_001278464.2 missense
NM_001278464.2 missense
Scores
3
7
8
Clinical Significance
Conservation
PhyloP100: 8.73
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, DNM1L
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNM1L | NM_001278464.2 | c.29A>G | p.Lys10Arg | missense_variant | 1/21 | ENST00000553257.6 | |
DNM1L | NM_012062.5 | c.29A>G | p.Lys10Arg | missense_variant | 1/20 | ENST00000549701.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNM1L | ENST00000553257.6 | c.29A>G | p.Lys10Arg | missense_variant | 1/21 | 2 | NM_001278464.2 | ||
DNM1L | ENST00000549701.6 | c.29A>G | p.Lys10Arg | missense_variant | 1/20 | 1 | NM_012062.5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461522Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727096
GnomAD4 exome
AF:
AC:
3
AN:
1461522
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
727096
Gnomad4 AFR exome
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Gnomad4 FIN exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
Alfa
AF:
Hom.:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2023 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 10 of the DNM1L protein (p.Lys10Arg). ClinVar contains an entry for this variant (Variation ID: 1381221). This variant has not been reported in the literature in individuals affected with DNM1L-related conditions. This variant is not present in population databases (gnomAD no frequency). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;L;L;.;L;.;.;L;L;.
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;N;N;N;N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T;T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T
Polyphen
0.12
.;.;B;.;.;.;.;.;.;.
Vest4
MutPred
Gain of catalytic residue at I5 (P = 7e-04);Gain of catalytic residue at I5 (P = 7e-04);Gain of catalytic residue at I5 (P = 7e-04);Gain of catalytic residue at I5 (P = 7e-04);Gain of catalytic residue at I5 (P = 7e-04);Gain of catalytic residue at I5 (P = 7e-04);Gain of catalytic residue at I5 (P = 7e-04);Gain of catalytic residue at I5 (P = 7e-04);Gain of catalytic residue at I5 (P = 7e-04);Gain of catalytic residue at I5 (P = 7e-04);
MVP
MPC
0.93
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