rs1060502816
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004281.4(BAG3):c.1160C>T(p.Pro387Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,614,058 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P387S) has been classified as Uncertain significance.
Frequency
Consequence
NM_004281.4 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 |
---|---|---|---|---|---|---|---|
BAG3 | NM_004281.4 | c.1160C>T | p.Pro387Leu | missense_variant | 4/4 | ENST00000369085.8 | |
BAG3 | XM_005270287.2 | c.1157C>T | p.Pro386Leu | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BAG3 | ENST00000369085.8 | c.1160C>T | p.Pro387Leu | missense_variant | 4/4 | 1 | NM_004281.4 | P1 | |
BAG3 | ENST00000450186.1 | downstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152180Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251384Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135902
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461878Hom.: 0 Cov.: 79 AF XY: 0.00 AC XY: 0AN XY: 727242
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152180Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74342
ClinVar
Submissions by phenotype
Myofibrillar myopathy 6;C3151293:Dilated cardiomyopathy 1HH Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 03, 2023 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BAG3 protein function. ClinVar contains an entry for this variant (Variation ID: 410236). This variant has not been reported in the literature in individuals affected with BAG3-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 387 of the BAG3 protein (p.Pro387Leu). - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 12, 2024 | The p.P387L variant (also known as c.1160C>T), located in coding exon 4 of the BAG3 gene, results from a C to T substitution at nucleotide position 1160. The proline at codon 387 is replaced by leucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at