chr10-99877204-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_015221.4(DNMBP):​c.4681G>C​(p.Gly1561Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

DNMBP
NM_015221.4 missense

Scores

11
6
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.63
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.905

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNMBPNM_015221.4 linkuse as main transcriptc.4681G>C p.Gly1561Arg missense_variant 17/17 ENST00000324109.9 NP_056036.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNMBPENST00000324109.9 linkuse as main transcriptc.4681G>C p.Gly1561Arg missense_variant 17/171 NM_015221.4 ENSP00000315659 P1Q6XZF7-1
DNMBPENST00000543621.6 linkuse as main transcriptc.2545G>C p.Gly849Arg missense_variant 14/141 ENSP00000443657
DNMBPENST00000636706.1 linkuse as main transcriptc.3577G>C p.Gly1193Arg missense_variant 14/142 ENSP00000489875

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 23, 2021The c.4681G>C (p.G1561R) alteration is located in exon 17 (coding exon 16) of the DNMBP gene. This alteration results from a G to C substitution at nucleotide position 4681, causing the glycine (G) at amino acid position 1561 to be replaced by an arginine (R). 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
0.36
BayesDel_addAF
Pathogenic
0.32
D
BayesDel_noAF
Pathogenic
0.22
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.30
.;.;T
Eigen
Pathogenic
0.90
Eigen_PC
Pathogenic
0.83
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Pathogenic
0.90
D;D;D
MetaSVM
Uncertain
0.22
D
MutationAssessor
Pathogenic
3.0
.;.;M
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.71
T
PROVEAN
Pathogenic
-6.5
.;.;D
REVEL
Pathogenic
0.74
Sift
Uncertain
0.0020
.;.;D
Sift4G
Pathogenic
0.0
.;.;D
Polyphen
1.0
.;.;D
Vest4
0.65
MVP
0.87
MPC
0.68
ClinPred
1.0
D
GERP RS
5.1
Varity_R
0.82
gMVP
0.80

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-101636961; API