rs61854624
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_032578.4(MYPN):c.1869C>A(p.Thr623=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,613,976 control chromosomes in the GnomAD database, including 21,862 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.13 ( 1677 hom., cov: 31)
Exomes 𝑓: 0.16 ( 20185 hom. )
Consequence
MYPN
NM_032578.4 synonymous
NM_032578.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0800
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
?
Variant 10-68166562-C-A is Benign according to our data. Variant chr10-68166562-C-A is described in ClinVar as [Benign]. Clinvar id is 31803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-68166562-C-A is described in Lovd as [Benign]. Variant chr10-68166562-C-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.08 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYPN | NM_032578.4 | c.1869C>A | p.Thr623= | synonymous_variant | 10/20 | ENST00000358913.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYPN | ENST00000358913.10 | c.1869C>A | p.Thr623= | synonymous_variant | 10/20 | 1 | NM_032578.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.129 AC: 19639AN: 152028Hom.: 1672 Cov.: 31
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GnomAD3 exomes AF: 0.165 AC: 41580AN: 251312Hom.: 3966 AF XY: 0.165 AC XY: 22413AN XY: 135824
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GnomAD4 exome AF: 0.161 AC: 234964AN: 1461830Hom.: 20185 Cov.: 77 AF XY: 0.161 AC XY: 117159AN XY: 727212
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GnomAD4 genome ? AF: 0.129 AC: 19660AN: 152146Hom.: 1677 Cov.: 31 AF XY: 0.132 AC XY: 9834AN XY: 74364
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ClinVar
Significance: Benign
Submissions summary: Benign:6Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 29, 2014 | p.Thr623Thr in exon 11 of MYPN: This variant is not expected to have clinical si gnificance because it has been identified in 17% (1492/8600) of European America n chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.ed u/EVS/; dbSNP rs61854624). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 22, 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 | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Dilated cardiomyopathy 1KK Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 12, 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. - |
not provided Other:1
not provided, no classification provided | curation | Leiden Muscular Dystrophy (MYPN) | Apr 27, 2012 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at