7-44057828-T-C

Variant summary

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

The NM_001014436.3(DBNL):ā€‹c.521T>Cā€‹(p.Val174Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000055 ( 0 hom. )

Consequence

DBNL
NM_001014436.3 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.73
Variant links:
Genes affected
DBNL (HGNC:2696): (drebrin like) Enables cadherin binding activity. Predicted to be involved in several processes, including Rac protein signal transduction; nervous system development; and podosome assembly. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.175089).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DBNLNM_001014436.3 linkuse as main transcriptc.521T>C p.Val174Ala missense_variant 6/13 ENST00000448521.6 NP_001014436.1 Q9UJU6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DBNLENST00000448521.6 linkuse as main transcriptc.521T>C p.Val174Ala missense_variant 6/131 NM_001014436.3 ENSP00000411701.1 Q9UJU6-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251346
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135896
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461870
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727240
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:
0.00000719
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 GeneticsOct 09, 2024The c.521T>C (p.V174A) alteration is located in exon 6 (coding exon 6) of the DBNL gene. This alteration results from a T to C substitution at nucleotide position 521, causing the valine (V) at amino acid position 174 to be replaced by an alanine (A). 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
0.18
BayesDel_addAF
Benign
-0.094
T
BayesDel_noAF
Benign
-0.37
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.093
T;.;.;.;T;.;.
Eigen
Benign
0.15
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.88
D;D;D;D;D;D;D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.18
T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.7
M;.;.;.;.;M;M
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-1.1
N;N;N;N;N;N;N
REVEL
Benign
0.058
Sift
Benign
0.17
T;T;T;T;T;T;T
Sift4G
Benign
0.46
T;T;T;T;T;T;T
Polyphen
0.86
P;.;.;.;P;P;P
Vest4
0.22
MutPred
0.24
Loss of stability (P = 0.0064);.;.;.;.;Loss of stability (P = 0.0064);Loss of stability (P = 0.0064);
MVP
0.67
MPC
0.29
ClinPred
0.66
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.17
gMVP
0.30

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: rs776930553; hg19: chr7-44097427; API