8-22630467-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_018688.6(BIN3):āc.272G>Cā(p.Arg91Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000874 in 1,613,914 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 (ā ).
Frequency
Genomes: š 0.000085 ( 0 hom., cov: 33)
Exomes š: 0.000088 ( 0 hom. )
Consequence
BIN3
NM_018688.6 missense
NM_018688.6 missense
Scores
6
7
6
Clinical Significance
Conservation
PhyloP100: 7.42
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 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.10782778).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BIN3 | NM_018688.6 | c.272G>C | p.Arg91Pro | missense_variant | 5/9 | ENST00000276416.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BIN3 | ENST00000276416.11 | c.272G>C | p.Arg91Pro | missense_variant | 5/9 | 1 | NM_018688.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152226Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000136 AC: 34AN: 249202Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135176
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GnomAD4 exome AF: 0.0000876 AC: 128AN: 1461688Hom.: 0 Cov.: 31 AF XY: 0.0000880 AC XY: 64AN XY: 727128
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GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152226Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7AN XY: 74370
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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 | Mar 07, 2023 | The c.272G>C (p.R91P) alteration is located in exon 5 (coding exon 5) of the BIN3 gene. This alteration results from a G to C substitution at nucleotide position 272, causing the arginine (R) at amino acid position 91 to be replaced by a proline (P). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;T;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
T
PROVEAN
Benign
N;N;N;D;.
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;.
Sift4G
Uncertain
D;D;D;D;.
Polyphen
D;.;.;.;.
Vest4
MVP
ClinPred
T
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