Menu
GeneBe

8-22630533-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018688.6(BIN3):c.206A>G(p.Asn69Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,613,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

BIN3
NM_018688.6 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.53
Variant links:
Genes affected
BIN3 (HGNC:1054): (bridging integrator 3) The product of this gene is a member of the BAR domain protein family. The encoded protein is comprised solely of a BAR domain which is predicted to form coiled-coil structures and proposed to mediate dimerization, sense and induce membrane curvature, and bind small GTPases. BAR domain proteins have been implicated in endocytosis, intracellular transport, and a diverse set of other processes. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.058100283).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BIN3NM_018688.6 linkuse as main transcriptc.206A>G p.Asn69Ser missense_variant 5/9 ENST00000276416.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BIN3ENST00000276416.11 linkuse as main transcriptc.206A>G p.Asn69Ser missense_variant 5/91 NM_018688.6 P1Q9NQY0-1

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152162
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000578
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000277
AC:
69
AN:
249246
Hom.:
0
AF XY:
0.000259
AC XY:
35
AN XY:
135210
show subpopulations
Gnomad AFR exome
AF:
0.0000646
Gnomad AMR exome
AF:
0.000464
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00139
Gnomad SAS exome
AF:
0.000392
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000124
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.000123
AC:
180
AN:
1461696
Hom.:
0
Cov.:
31
AF XY:
0.000121
AC XY:
88
AN XY:
727130
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.000358
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000982
Gnomad4 SAS exome
AF:
0.000313
Gnomad4 FIN exome
AF:
0.0000936
Gnomad4 NFE exome
AF:
0.0000693
Gnomad4 OTH exome
AF:
0.000133
GnomAD4 genome
AF:
0.000125
AC:
19
AN:
152280
Hom.:
0
Cov.:
33
AF XY:
0.000148
AC XY:
11
AN XY:
74460
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000579
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000880
Hom.:
0
Bravo
AF:
0.0000945
ExAC
AF:
0.000199
AC:
24
Asia WGS
AF:
0.00115
AC:
4
AN:
3478

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 GeneticsFeb 07, 2023The c.206A>G (p.N69S) alteration is located in exon 5 (coding exon 5) of the BIN3 gene. This alteration results from a A to G substitution at nucleotide position 206, causing the asparagine (N) at amino acid position 69 to be replaced by a serine (S). 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
0.12
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.34
Cadd
Benign
22
Dann
Uncertain
1.0
DEOGEN2
Benign
0.19
T;.;T;T;.
Eigen
Uncertain
0.26
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.95
D;D;D;D;D
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.058
T;T;T;T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Uncertain
2.2
M;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-1.2
N;N;N;N;.
REVEL
Benign
0.14
Sift
Benign
0.20
T;T;T;T;.
Sift4G
Benign
0.10
T;T;T;D;.
Polyphen
0.45
B;.;.;.;.
Vest4
0.81
MutPred
0.51
Gain of phosphorylation at S68 (P = 0.1065);.;.;Gain of phosphorylation at S68 (P = 0.1065);Gain of phosphorylation at S68 (P = 0.1065);
MVP
0.52
ClinPred
0.11
T
GERP RS
5.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.11
gMVP
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs368195300; hg19: chr8-22488046; API