chr1-172044448-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015569.5(DNM3):c.1192A>G(p.Ile398Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000125 in 1,605,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
DNM3
NM_015569.5 missense
NM_015569.5 missense
Scores
1
1
16
Clinical Significance
Conservation
PhyloP100: 3.61
Genes affected
DNM3 (HGNC:29125): (dynamin 3) This gene encodes a member of a family of guanosine triphosphate (GTP)-binding proteins that associate with microtubules and are involved in vesicular transport. The encoded protein functions in the development of megakaryocytes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.12133533).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNM3 | NM_015569.5 | c.1192A>G | p.Ile398Val | missense_variant | 9/21 | ENST00000627582.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNM3 | ENST00000627582.3 | c.1192A>G | p.Ile398Val | missense_variant | 9/21 | 1 | NM_015569.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152230Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000212 AC: 5AN: 236102Hom.: 0 AF XY: 0.00000786 AC XY: 1AN XY: 127242
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GnomAD4 exome AF: 0.00000482 AC: 7AN: 1453160Hom.: 0 Cov.: 30 AF XY: 0.00000554 AC XY: 4AN XY: 721748
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GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152230Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74372
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 14, 2021 | The c.1192A>G (p.I398V) alteration is located in exon 9 (coding exon 9) of the DNM3 gene. This alteration results from a A to G substitution at nucleotide position 1192, causing the isoleucine (I) at amino acid position 398 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;N;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;.;N;N;N
REVEL
Benign
Sift
Benign
T;T;.;T;T;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
0.0, 0.0010
.;.;B;B;B;.
Vest4
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at