5-177458587-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.1385G>A​(p.Ser462Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Consequence

DBN1
NM_001363541.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.99
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]

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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=0.116832614).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DBN1NM_001363541.2 linkc.1385G>A p.Ser462Asn 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.1385G>A p.Ser462Asn missense_variant Exon 13 of 15 5 NM_001363541.2 ENSP00000377195.1 Q16643-3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
36
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 27, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1253G>A (p.S418N) 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 1253, causing the serine (S) at amino acid position 418 to be replaced by an asparagine (N). 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
0.084
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
18
DANN
Benign
0.78
DEOGEN2
Benign
0.11
T;.;.;T
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.36
FATHMM_MKL
Benign
0.40
N
LIST_S2
Benign
0.79
T;T;T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.12
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.90
L;.;.;.
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-0.50
N;N;N;N
REVEL
Benign
0.095
Sift
Benign
0.30
T;T;D;T
Sift4G
Benign
0.23
T;T;T;T
Polyphen
0.12
B;B;.;.
Vest4
0.16
MutPred
0.20
Loss of glycosylation at S416 (P = 0.009);.;.;.;
MVP
0.40
MPC
0.12
ClinPred
0.16
T
GERP RS
4.2
Varity_R
0.12
gMVP
0.092

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: rs1756749566; hg19: chr5-176885588; API