chr10-99880232-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_015221.4(DNMBP):c.4127G>A(p.Arg1376His) variant causes a missense change. The variant allele was found at a frequency of 0.0000248 in 1,613,898 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
DNMBP
NM_015221.4 missense
NM_015221.4 missense
Scores
4
6
9
Clinical Significance
Conservation
PhyloP100: 4.74
Genes affected
DNMBP (HGNC:30373): (dynamin binding protein) This gene encodes a protein belonging to the guanine nucleotide exchange factor family, and which regulates the configuration of cell junctions. It contains multiple binding sites for dynamin and thus links dynamin to actin regulatory proteins. Polymorphisms in this gene have been linked to Alzheimer's disease in some populations, though there are conflicting reports of such linkages in other populations. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNMBP | NM_015221.4 | c.4127G>A | p.Arg1376His | missense_variant | 16/17 | ENST00000324109.9 | NP_056036.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNMBP | ENST00000324109.9 | c.4127G>A | p.Arg1376His | missense_variant | 16/17 | 1 | NM_015221.4 | ENSP00000315659 | P1 | |
DNMBP | ENST00000543621.6 | c.1991G>A | p.Arg664His | missense_variant | 13/14 | 1 | ENSP00000443657 | |||
DNMBP | ENST00000636706.1 | c.3023G>A | p.Arg1008His | missense_variant | 13/14 | 2 | ENSP00000489875 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152056Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251368Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135862
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GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461842Hom.: 0 Cov.: 33 AF XY: 0.0000261 AC XY: 19AN XY: 727222
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152056Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74268
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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 | Mar 08, 2024 | The c.4127G>A (p.R1376H) alteration is located in exon 16 (coding exon 15) of the DNMBP gene. This alteration results from a G to A substitution at nucleotide position 4127, causing the arginine (R) at amino acid position 1376 to be replaced by a histidine (H). 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
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
.;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;.;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
.;.;N
REVEL
Benign
Sift
Uncertain
.;.;D
Sift4G
Uncertain
.;.;D
Polyphen
1.0
.;.;D
Vest4
0.47
MVP
MPC
0.65
ClinPred
D
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