rs72546667
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1
The NM_033337.3(CAV3):c.166G>A(p.Gly56Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00644 in 1,614,038 control chromosomes in the GnomAD database, including 549 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G56G) has been classified as Likely benign.
Frequency
Consequence
NM_033337.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAV3 | NM_033337.3 | c.166G>A | p.Gly56Ser | missense_variant | 2/2 | ENST00000343849.3 | |
CAV3 | NM_001234.5 | c.166G>A | p.Gly56Ser | missense_variant | 2/3 | ||
OXTR | XR_007095681.1 | n.1885-2975C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAV3 | ENST00000343849.3 | c.166G>A | p.Gly56Ser | missense_variant | 2/2 | 1 | NM_033337.3 | P1 | |
CAV3 | ENST00000397368.2 | c.166G>A | p.Gly56Ser | missense_variant | 2/3 | 1 | P1 | ||
CAV3 | ENST00000472766.1 | n.155+11587G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0330 AC: 5021AN: 152078Hom.: 264 Cov.: 32
GnomAD3 exomes AF: 0.00888 AC: 2233AN: 251334Hom.: 140 AF XY: 0.00640 AC XY: 869AN XY: 135834
GnomAD4 exome AF: 0.00366 AC: 5357AN: 1461842Hom.: 283 Cov.: 32 AF XY: 0.00321 AC XY: 2333AN XY: 727226
GnomAD4 genome ? AF: 0.0331 AC: 5036AN: 152196Hom.: 266 Cov.: 32 AF XY: 0.0317 AC XY: 2356AN XY: 74416
ClinVar
Submissions by phenotype
not specified Benign:9
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 28, 2017 | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 01, 2013 | - - |
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 | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 10, 2012 | Gly56Ser in exon 2 of CAV3: This variant is not expected to have clinical signif icance because it has been identified in 10.9% (407/3738) of African American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS/; dbSNP rs72546667) - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 11, 2011 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:3Other:1
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Sep 08, 2016 | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
not provided, no classification provided | literature only | Leiden Muscular Dystrophy (CAV3) | - | - - |
Rippling muscle disease 2 Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | OMIM | Jan 01, 2005 | - - |
Elevated circulating creatine kinase concentration;C1832560:Rippling muscle disease 2;C2678485:Long QT syndrome 9;C3280443:Distal myopathy, Tateyama type;C3495498:Hypertrophic cardiomyopathy 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 18, 2022 | - - |
Long QT syndrome 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Limb-Girdle Muscular Dystrophy, Dominant Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Jul 31, 2020 | - - |
Caveolinopathy Benign:1
Likely benign, 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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Limb-girdle muscular dystrophy Benign:1
Benign, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Long QT syndrome 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 | Jul 16, 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