rs766084373
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_004281.4(BAG3):āc.372T>Gā(p.Thr124=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,102 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 Likely benign (ā ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 33)
Exomes š: 0.0000027 ( 0 hom. )
Consequence
BAG3
NM_004281.4 synonymous
NM_004281.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.83
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 Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 10-119670042-T-G is Benign according to our data. Variant chr10-119670042-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 539164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.83 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BAG3 | NM_004281.4 | c.372T>G | p.Thr124= | synonymous_variant | 2/4 | ENST00000369085.8 | |
BAG3 | XM_005270287.2 | c.372T>G | p.Thr124= | synonymous_variant | 2/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BAG3 | ENST00000369085.8 | c.372T>G | p.Thr124= | synonymous_variant | 2/4 | 1 | NM_004281.4 | P1 | |
BAG3 | ENST00000450186.1 | c.198T>G | p.Thr66= | synonymous_variant | 3/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461876Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727240
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74372
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Myofibrillar myopathy 6;C3151293:Dilated cardiomyopathy 1HH Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 08, 2023 | - - |
BAG3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 12, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at