rs746551805
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS2
The NM_004281.4(BAG3):c.773G>A(p.Arg258Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,688 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. R258W) has been classified as Benign.
Frequency
Consequence
NM_004281.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BAG3 | NM_004281.4 | c.773G>A | p.Arg258Gln | missense_variant | 3/4 | ENST00000369085.8 | NP_004272.2 | |
BAG3 | XM_005270287.2 | c.773G>A | p.Arg258Gln | missense_variant | 3/4 | XP_005270344.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BAG3 | ENST00000369085.8 | c.773G>A | p.Arg258Gln | missense_variant | 3/4 | 1 | NM_004281.4 | ENSP00000358081.4 | ||
BAG3 | ENST00000450186.1 | c.599G>A | p.Arg200Gln | missense_variant | 4/5 | 5 | ENSP00000410036.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250530Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135490
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461688Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727124
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Myofibrillar myopathy 6;C3151293:Dilated cardiomyopathy 1HH Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 16, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 258 of the BAG3 protein (p.Arg258Gln). This variant is present in population databases (rs746551805, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with BAG3-related conditions. ClinVar contains an entry for this variant (Variation ID: 539162). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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