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GeneBe

8-22630001-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018688.6(BIN3):c.301A>G(p.Asn101Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000106 in 1,609,500 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

BIN3
NM_018688.6 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.69
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27111328).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BIN3NM_018688.6 linkuse as main transcriptc.301A>G p.Asn101Asp missense_variant 6/9 ENST00000276416.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BIN3ENST00000276416.11 linkuse as main transcriptc.301A>G p.Asn101Asp missense_variant 6/91 NM_018688.6 P1Q9NQY0-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152216
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000416
AC:
1
AN:
240440
Hom.:
0
AF XY:
0.00000766
AC XY:
1
AN XY:
130534
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000296
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1457284
Hom.:
0
Cov.:
32
AF XY:
0.0000138
AC XY:
10
AN XY:
724448
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000227
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:
0.0000135
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152216
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

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 04, 2022The c.301A>G (p.N101D) alteration is located in exon 6 (coding exon 6) of the BIN3 gene. This alteration results from a A to G substitution at nucleotide position 301, causing the asparagine (N) at amino acid position 101 to be replaced by an aspartic acid (D). 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
0.47
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
Cadd
Uncertain
24
Dann
Uncertain
1.0
DEOGEN2
Benign
0.12
T;.;T;T;.
Eigen
Benign
0.037
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.81
T;T;T;T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.27
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
0.44
N;N;N;N;.
REVEL
Benign
0.10
Sift
Benign
0.044
D;T;T;T;.
Sift4G
Benign
0.35
T;T;T;T;.
Polyphen
0.084
B;.;.;.;.
Vest4
0.74
MutPred
0.61
Gain of ubiquitination at K105 (P = 0.0758);.;.;Gain of ubiquitination at K105 (P = 0.0758);Gain of ubiquitination at K105 (P = 0.0758);
MVP
0.57
ClinPred
0.43
T
GERP RS
5.6
Varity_R
0.26
gMVP
0.45

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: rs1473161841; hg19: chr8-22487514; API