rs780918654
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_139343.3(BIN1):c.1439C>T(p.Thr480Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,396 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T480K) has been classified as Uncertain significance.
Frequency
Consequence
NM_139343.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BIN1 | NM_139343.3 | c.1439C>T | p.Thr480Met | missense_variant | 16/19 | ENST00000316724.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BIN1 | ENST00000316724.10 | c.1439C>T | p.Thr480Met | missense_variant | 16/19 | 1 | NM_139343.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152192Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000321 AC: 8AN: 249368Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135236
GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461204Hom.: 0 Cov.: 33 AF XY: 0.0000165 AC XY: 12AN XY: 726926
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152192Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74354
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2021 | The c.1439C>T (p.T480M) alteration is located in exon 16 (coding exon 16) of the BIN1 gene. This alteration results from a C to T substitution at nucleotide position 1439, causing the threonine (T) at amino acid position 480 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 02, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Myopathy, centronuclear, 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2024 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 480 of the BIN1 protein (p.Thr480Met). This variant is present in population databases (rs780918654, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with BIN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 461705). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at