rs71584491
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_032578.4(MYPN):c.2163C>A(p.Ala721=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 1,613,986 control chromosomes in the GnomAD database, including 761 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.041 ( 303 hom., cov: 31)
Exomes 𝑓: 0.016 ( 458 hom. )
Consequence
MYPN
NM_032578.4 synonymous
NM_032578.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.687
Genes affected
MYPN (HGNC:23246): (myopalladin) Striated muscle in vertebrates comprises large proteins which must be organized properly to contract efficiently. Z-lines in striated muscle are a sign of this organization, representing the ends of actin thin filaments, titin, nebulin or nebulette and accessory proteins required for structure and function. This gene encodes a protein which interacts with nebulin in skeletal muscle or nebulette in cardiac muscle and alpha-actinin. In addition, this gene product can interact with a protein with the I-band indicating it has a regulatory as well as structural function. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
Variant 10-68174255-C-A is Benign according to our data. Variant chr10-68174255-C-A is described in ClinVar as [Benign]. Clinvar id is 31806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-68174255-C-A is described in Lovd as [Benign]. Variant chr10-68174255-C-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=0.687 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYPN | NM_032578.4 | c.2163C>A | p.Ala721= | synonymous_variant | 11/20 | ENST00000358913.10 | NP_115967.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYPN | ENST00000358913.10 | c.2163C>A | p.Ala721= | synonymous_variant | 11/20 | 1 | NM_032578.4 | ENSP00000351790 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0403 AC: 6132AN: 151982Hom.: 299 Cov.: 31
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GnomAD3 exomes AF: 0.0217 AC: 5445AN: 251444Hom.: 141 AF XY: 0.0212 AC XY: 2887AN XY: 135892
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GnomAD4 exome AF: 0.0163 AC: 23776AN: 1461886Hom.: 458 Cov.: 75 AF XY: 0.0167 AC XY: 12127AN XY: 727246
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GnomAD4 genome AF: 0.0405 AC: 6162AN: 152100Hom.: 303 Cov.: 31 AF XY: 0.0396 AC XY: 2944AN XY: 74366
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ClinVar
Significance: Benign
Submissions summary: Benign:9Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:6
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 13, 2015 | p.Ala721Ala in exon 12 of MYPN: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 10.4% (458/4406) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs71584491). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 17, 2013 | 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. - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute | May 13, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 17, 2023 | - - |
not provided Benign:1Other:1
not provided, no classification provided | curation | Leiden Muscular Dystrophy (MYPN) | Apr 27, 2012 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Dilated cardiomyopathy 1KK Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 19, 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
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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