5-177458675-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001363541.2(DBN1):​c.1297G>A​(p.Glu433Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000166 in 1,562,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

DBN1
NM_001363541.2 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.759
Variant links:
Genes affected
DBN1 (HGNC:2695): (drebrin 1) The protein encoded by this gene is a cytoplasmic actin-binding protein thought to play a role in the process of neuronal growth. It is a member of the drebrin family of proteins that are developmentally regulated in the brain. A decrease in the amount of this protein in the brain has been implicated as a possible contributing factor in the pathogenesis of memory disturbance in Alzheimer's disease. At least two alternative splice variants encoding different protein isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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=0.077875525).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DBN1NM_001363541.2 linkc.1297G>A p.Glu433Lys missense_variant Exon 13 of 15 ENST00000393565.6 NP_001350470.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DBN1ENST00000393565.6 linkc.1297G>A p.Glu433Lys missense_variant Exon 13 of 15 5 NM_001363541.2 ENSP00000377195.1 Q16643-3

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152210
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000210
AC:
4
AN:
190394
Hom.:
0
AF XY:
0.0000195
AC XY:
2
AN XY:
102784
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000461
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000163
AC:
23
AN:
1410404
Hom.:
0
Cov.:
35
AF XY:
0.0000100
AC XY:
7
AN XY:
698032
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.0000193
Gnomad4 OTH exome
AF:
0.0000345
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152210
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.00000830
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 19, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1165G>A (p.E389K) alteration is located in exon 13 (coding exon 12) of the DBN1 gene. This alteration results from a G to A substitution at nucleotide position 1165, causing the glutamic acid (E) at amino acid position 389 to be replaced by a lysine (K). 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
Benign
0.062
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
T;.;.;T
Eigen
Benign
-0.56
Eigen_PC
Benign
-0.44
FATHMM_MKL
Benign
0.25
N
LIST_S2
Benign
0.85
D;D;D;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.078
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.14
N;.;.;.
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-1.1
N;N;N;N
REVEL
Benign
0.048
Sift
Benign
0.058
T;T;D;T
Sift4G
Benign
0.18
T;T;T;T
Polyphen
0.14
B;B;.;.
Vest4
0.15
MutPred
0.22
Gain of ubiquitination at E387 (P = 0.0054);.;.;.;
MVP
0.32
MPC
0.15
ClinPred
0.053
T
GERP RS
3.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.064
gMVP
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs746526803; hg19: chr5-176885676; API