9-128218658-G-A
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_004408.4(DNM1):c.312G>A(p.Glu104Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.072 in 1,613,176 control chromosomes in the GnomAD database, including 5,489 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.11 ( 1342 hom., cov: 31)
Exomes 𝑓: 0.068 ( 4147 hom. )
Consequence
DNM1
NM_004408.4 synonymous
NM_004408.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.62
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 -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.2).
BP6
Variant 9-128218658-G-A is Benign according to our data. Variant chr9-128218658-G-A is described in ClinVar as [Benign]. Clinvar id is 380778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.62 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
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DNM1 | ENST00000372923.8 | c.312G>A | p.Glu104Glu | synonymous_variant | 3/22 | 1 | NM_004408.4 | ENSP00000362014.4 | ||
DNM1 | ENST00000634267.2 | c.312G>A | p.Glu104Glu | synonymous_variant | 3/22 | 5 | ENSP00000489096.1 |
Frequencies
GnomAD3 genomes AF: 0.109 AC: 16569AN: 151940Hom.: 1335 Cov.: 31
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GnomAD3 exomes AF: 0.0717 AC: 17944AN: 250324Hom.: 1001 AF XY: 0.0713 AC XY: 9652AN XY: 135422
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GnomAD4 exome AF: 0.0681 AC: 99515AN: 1461118Hom.: 4147 Cov.: 33 AF XY: 0.0686 AC XY: 49865AN XY: 726746
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GnomAD4 genome AF: 0.109 AC: 16605AN: 152058Hom.: 1342 Cov.: 31 AF XY: 0.105 AC XY: 7827AN XY: 74326
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 31A Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 03, 2025 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 07, 2016 | 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. - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 31, 2015 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at