2-127057558-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_139343.3(BIN1):c.1046C>T(p.Pro349Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000777 in 1,543,428 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P349P) has been classified as Likely benign.
Frequency
Consequence
NM_139343.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BIN1 | NM_139343.3 | c.1046C>T | p.Pro349Leu | missense_variant | 12/19 | ENST00000316724.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BIN1 | ENST00000316724.10 | c.1046C>T | p.Pro349Leu | missense_variant | 12/19 | 1 | NM_139343.3 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152036Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.00000719 AC: 10AN: 1391392Hom.: 0 Cov.: 30 AF XY: 0.00000584 AC XY: 4AN XY: 685018
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152036Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74236
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 27, 2023 | The c.1046C>T (p.P349L) alteration is located in exon 12 (coding exon 12) of the BIN1 gene. This alteration results from a C to T substitution at nucleotide position 1046, causing the proline (P) at amino acid position 349 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Myopathy, centronuclear, 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 23, 2023 | This variant has not been reported in the literature in individuals affected with BIN1-related conditions. 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. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 583021). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 349 of the BIN1 protein (p.Pro349Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at