rs144692954
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_004281.4(BAG3):c.1138C>T(p.Pro380Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000742 in 1,614,136 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P380L) has been classified as Uncertain significance.
Frequency
Consequence
NM_004281.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BAG3 | NM_004281.4 | c.1138C>T | p.Pro380Ser | missense_variant | 4/4 | ENST00000369085.8 | |
BAG3 | XM_005270287.2 | c.1135C>T | p.Pro379Ser | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BAG3 | ENST00000369085.8 | c.1138C>T | p.Pro380Ser | missense_variant | 4/4 | 1 | NM_004281.4 | P1 | |
BAG3 | ENST00000450186.1 | c.961C>T | p.Pro321Ser | missense_variant | 5/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00307 AC: 467AN: 152128Hom.: 2 Cov.: 31
GnomAD3 exomes AF: 0.00126 AC: 318AN: 251448Hom.: 2 AF XY: 0.00107 AC XY: 145AN XY: 135906
GnomAD4 exome AF: 0.000499 AC: 730AN: 1461890Hom.: 7 Cov.: 79 AF XY: 0.000523 AC XY: 380AN XY: 727248
GnomAD4 genome ? AF: 0.00307 AC: 467AN: 152246Hom.: 2 Cov.: 31 AF XY: 0.00265 AC XY: 197AN XY: 74446
ClinVar
Submissions by phenotype
not specified Benign:7
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 19, 2012 | p.Pro380Ser in Exon 04 of BAG3: This variant is not expected to have clinical si gnificance because it has been identified in 1.0% (39/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs144692954). - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 18, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 04, 2017 | Variant summary: The BAG3 c.1138C>T (p.Pro380Ser) variant involves the alteration of a non-conserved nucleotide. 2/3 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 180/121378 control chromosomes (2 homozygotes) from ExAC, predominantly observed in the African subpopulation at a frequency of 0.010959 (114/10402). This frequency is about 281 times the estimated maximal expected allele frequency of a pathogenic BAG3 variant (0.0000391), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories in ClinVar have classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals in literature. Taken together, this variant is classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 16, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 09, 2018 | This variant is associated with the following publications: (PMID: 27896284, 21459883) - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jul 22, 2016 | - - |
Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | May 16, 2023 | - - |
Myofibrillar myopathy 6 Benign:1
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Atrial fibrillation Benign:1
Benign, criteria provided, single submitter | clinical testing | Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego | Apr 17, 2019 | - - |
Myofibrillar myopathy 6;C3151293:Dilated cardiomyopathy 1HH Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 20, 2015 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at