rs786205457
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_032578.4(MYPN):c.935C>T(p.Ser312Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
MYPN
NM_032578.4 missense
NM_032578.4 missense
Scores
6
11
2
Clinical Significance
Conservation
PhyloP100: 4.98
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 Uncertain_significance. Variant got 5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.842
PP5
Variant 10-68142972-C-T is Pathogenic according to our data. Variant chr10-68142972-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 191001.We mark this variant Likely_pathogenic, oryginal submissions are: {Likely_pathogenic=1, Uncertain_significance=2}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYPN | NM_032578.4 | c.935C>T | p.Ser312Phe | missense_variant | 3/20 | ENST00000358913.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYPN | ENST00000358913.10 | c.935C>T | p.Ser312Phe | missense_variant | 3/20 | 1 | NM_032578.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | - | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 04, 2015 | The p.Ser312Phe variant in MYPN has not been previously reported in individuals with cardiomyopathy and was absent from large population studies. Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predictive enough to determine patho genicity. In summary, the clinical significance of the p.Ser312Phe variant is un certain. - |
Hypertrophic cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Genetics and Genomics Program, Sidra Medicine | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;.;.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;.;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;M;.;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;.;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;.;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
D;D;D;.;D
Vest4
MutPred
Loss of disorder (P = 0.0062);.;Loss of disorder (P = 0.0062);.;Loss of disorder (P = 0.0062);
MVP
MPC
0.64
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at