rs772239774
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP6_Very_Strong
The NM_004408.4(DNM1):c.1772C>T(p.Thr591Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000731 in 1,613,554 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000073 ( 0 hom. )
Consequence
DNM1
NM_004408.4 missense
NM_004408.4 missense
Scores
6
9
4
Clinical Significance
Conservation
PhyloP100: 7.77
Genes affected
DNM1 (HGNC:2972): (dynamin 1) This gene encodes a member of the dynamin subfamily of GTP-binding proteins. The encoded protein possesses unique mechanochemical properties used to tubulate and sever membranes, and is involved in clathrin-mediated endocytosis and other vesicular trafficking processes. Actin and other cytoskeletal proteins act as binding partners for the encoded protein, which can also self-assemble leading to stimulation of GTPase activity. More than sixty highly conserved copies of the 3' region of this gene are found elsewhere in the genome, particularly on chromosomes Y and 15. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DNM1. . Gene score misZ 5.1795 (greater than the threshold 3.09). Trascript score misZ 5.021 (greater than threshold 3.09). GenCC has associacion of gene with developmental and epileptic encephalopathy, 31, undetermined early-onset epileptic encephalopathy, developmental and epileptic encephalopathy 31B, developmental and epileptic encephalopathy, Lennox-Gastaut syndrome.
BP6
Variant 9-128246494-C-T is Benign according to our data. Variant chr9-128246494-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 476062.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNM1 | NM_004408.4 | c.1772C>T | p.Thr591Met | missense_variant | 16/22 | ENST00000372923.8 | NP_004399.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNM1 | ENST00000372923.8 | c.1772C>T | p.Thr591Met | missense_variant | 16/22 | 1 | NM_004408.4 | ENSP00000362014.4 | ||
DNM1 | ENST00000634267.2 | c.1772C>T | p.Thr591Met | missense_variant | 16/22 | 5 | ENSP00000489096.1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152152Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000756 AC: 19AN: 251390Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135874
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GnomAD4 exome AF: 0.0000732 AC: 107AN: 1461402Hom.: 0 Cov.: 30 AF XY: 0.0000784 AC XY: 57AN XY: 727064
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GnomAD4 genome AF: 0.0000723 AC: 11AN: 152152Hom.: 0 Cov.: 31 AF XY: 0.0000673 AC XY: 5AN XY: 74310
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | DNM1: PP2, PP3, BS1 - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Developmental and epileptic encephalopathy, 31A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 07, 2023 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 20, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;.;.;.;.;.;T;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;.;.;D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;M;M;.;M;.;M;.
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;D;.;D;.;.;.
REVEL
Pathogenic
Sift
Benign
D;D;D;D;.;D;.;.;.
Sift4G
Benign
T;T;T;T;T;T;T;T;T
Polyphen
D;.;D;.;.;.;.;D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at