rs138218523
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_003476.5(CSRP3):c.299G>A(p.Arg100His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000769 in 1,614,156 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R100C) has been classified as Uncertain significance.
Frequency
Consequence
NM_003476.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CSRP3 | NM_003476.5 | c.299G>A | p.Arg100His | missense_variant | 4/6 | ENST00000265968.9 | |
CSRP3 | NM_001369404.1 | c.130G>A | p.Ala44Thr | missense_variant | 3/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CSRP3 | ENST00000265968.9 | c.299G>A | p.Arg100His | missense_variant | 4/6 | 1 | NM_003476.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000907 AC: 138AN: 152156Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00117 AC: 294AN: 251360Hom.: 1 AF XY: 0.00116 AC XY: 157AN XY: 135854
GnomAD4 exome AF: 0.000755 AC: 1103AN: 1461882Hom.: 3 Cov.: 32 AF XY: 0.000755 AC XY: 549AN XY: 727242
GnomAD4 genome ? AF: 0.000906 AC: 138AN: 152274Hom.: 1 Cov.: 32 AF XY: 0.000940 AC XY: 70AN XY: 74448
ClinVar
Submissions by phenotype
not provided Benign:5
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 16, 2020 | In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23299917, 24082139, 19035361, 23861362, 30012424) - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Aug 24, 2017 | - - |
not specified Uncertain:1Benign:3
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 06, 2012 | Variant classified as Uncertain Significance - Favor Benign. The Arg100His varia nt (CSRP3) has been reported in 1 individual with HCM (Anderson 2009) and has be en detected in 1 individual with HCM tested by our laboratory who carried a path ogenic HCM variant (LMM unpublished data). This variant has been identified in 0.1% (6/7020) of European American chromosomes from a broad population by the NH LBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs13821852 3). While this frequency suggests that it is more likely benign but it is too lo w to confidently rule out a disease causing role. Additional information is need ed to fully assess its clinical significance. - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Apr 07, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Blueprint Genetics | Jan 19, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Oct 02, 2021 | - - |
Hypertrophic cardiomyopathy 12 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
CSRP3-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 05, 2020 | 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). - |
Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | May 04, 2018 | - - |
Dilated cardiomyopathy 1M;C2677491:Hypertrophic cardiomyopathy 12 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Hypertrophic cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Apr 05, 2018 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 05, 2019 | This alteration is classified as likely 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