10-119672293-ATCC-ATCCTCCTCC
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_004281.4(BAG3):c.549_554dupCTCCTC(p.Ser184_Ser185dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,184 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
BAG3
NM_004281.4 disruptive_inframe_insertion
NM_004281.4 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.51
Genes affected
BAG3 (HGNC:939): (BAG cochaperone 3) BAG proteins compete with Hip for binding to the Hsc70/Hsp70 ATPase domain and promote substrate release. All the BAG proteins have an approximately 45-amino acid BAG domain near the C terminus but differ markedly in their N-terminal regions. The protein encoded by this gene contains a WW domain in the N-terminal region and a BAG domain in the C-terminal region. The BAG domains of BAG1, BAG2, and BAG3 interact specifically with the Hsc70 ATPase domain in vitro and in mammalian cells. All 3 proteins bind with high affinity to the ATPase domain of Hsc70 and inhibit its chaperone activity in a Hip-repressible manner. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_004281.4.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| BAG3 | NM_004281.4 | c.549_554dupCTCCTC | p.Ser184_Ser185dup | disruptive_inframe_insertion | 3/4 | ENST00000369085.8 | NP_004272.2 | |
| BAG3 | XM_005270287.2 | c.549_554dupCTCCTC | p.Ser184_Ser185dup | disruptive_inframe_insertion | 3/4 | XP_005270344.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| BAG3 | ENST00000369085.8 | c.549_554dupCTCCTC | p.Ser184_Ser185dup | disruptive_inframe_insertion | 3/4 | 1 | NM_004281.4 | ENSP00000358081.4 | ||
| BAG3 | ENST00000450186.1 | c.375_380dupCTCCTC | p.Ser126_Ser127dup | disruptive_inframe_insertion | 4/5 | 5 | ENSP00000410036.1 |
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 152066Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249364Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135230
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GnomAD4 genome 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74398
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ClinVar
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at