8-22624319-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_018688.6(BIN3):c.383G>A(p.Arg128Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,613,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000038 ( 0 hom. )
Consequence
BIN3
NM_018688.6 missense
NM_018688.6 missense
Scores
11
7
1
Clinical Significance
Conservation
PhyloP100: 7.79
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 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.89
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BIN3 | NM_018688.6 | c.383G>A | p.Arg128Gln | missense_variant | 7/9 | ENST00000276416.11 | |
BIN3 | NM_001363046.2 | c.239G>A | p.Arg80Gln | missense_variant | 6/8 | ||
BIN3 | XM_047421995.1 | c.221G>A | p.Arg74Gln | missense_variant | 4/6 | ||
BIN3 | NR_156436.2 | n.453G>A | non_coding_transcript_exon_variant | 7/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BIN3 | ENST00000276416.11 | c.383G>A | p.Arg128Gln | missense_variant | 7/9 | 1 | NM_018688.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152210Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000402 AC: 10AN: 248906Hom.: 0 AF XY: 0.0000740 AC XY: 10AN XY: 135092
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GnomAD4 exome AF: 0.0000376 AC: 55AN: 1461602Hom.: 0 Cov.: 33 AF XY: 0.0000481 AC XY: 35AN XY: 727088
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152210Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74360
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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 submitter | clinical testing | Ambry Genetics | Nov 21, 2022 | The c.383G>A (p.R128Q) alteration is located in exon 7 (coding exon 7) of the BIN3 gene. This alteration results from a G to A substitution at nucleotide position 383, causing the arginine (R) at amino acid position 128 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Pathogenic
D;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;.;.
Vest4
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at