chr10-99880314-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015221.4(DNMBP):ā€‹c.4045C>Gā€‹(p.Arg1349Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000745 in 1,611,404 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000046 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

DNMBP
NM_015221.4 missense

Scores

2
12
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.95
Variant links:
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]

Genome browser will be placed here

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
DNMBPNM_015221.4 linkuse as main transcriptc.4045C>G p.Arg1349Gly missense_variant 16/17 ENST00000324109.9 NP_056036.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNMBPENST00000324109.9 linkuse as main transcriptc.4045C>G p.Arg1349Gly missense_variant 16/171 NM_015221.4 ENSP00000315659 P1Q6XZF7-1
DNMBPENST00000543621.6 linkuse as main transcriptc.1909C>G p.Arg637Gly missense_variant 13/141 ENSP00000443657
DNMBPENST00000636706.1 linkuse as main transcriptc.2941C>G p.Arg981Gly missense_variant 13/142 ENSP00000489875

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152194
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000811
AC:
2
AN:
246616
Hom.:
0
AF XY:
0.00000748
AC XY:
1
AN XY:
133706
show subpopulations
Gnomad AFR exome
AF:
0.000128
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000343
AC:
5
AN:
1459210
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
725726
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152194
Hom.:
0
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.000169
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000302
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsAug 17, 2021The c.4045C>G (p.R1349G) alteration is located in exon 16 (coding exon 15) of the DNMBP gene. This alteration results from a C to G substitution at nucleotide position 4045, causing the arginine (R) at amino acid position 1349 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.50
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Pathogenic
0.20
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.21
.;.;T
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Uncertain
0.093
D
MetaRNN
Uncertain
0.73
D;D;D
MetaSVM
Benign
-0.75
T
MutationAssessor
Benign
1.9
.;.;L
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-2.9
.;.;D
REVEL
Uncertain
0.39
Sift
Benign
0.055
.;.;T
Sift4G
Uncertain
0.015
.;.;D
Polyphen
1.0
.;.;D
Vest4
0.60
MVP
0.80
MPC
0.71
ClinPred
0.95
D
GERP RS
5.4
Varity_R
0.29
gMVP
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs372427020; hg19: chr10-101640071; API