rs199476407
Positions:
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP7BS1_SupportingBS2
The NM_032578.4(MYPN):āc.1419T>Cā(p.Thr473Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000827 in 1,450,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000083 ( 0 hom. )
Consequence
MYPN
NM_032578.4 synonymous
NM_032578.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.412
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 -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP7
Synonymous conserved (PhyloP=0.412 with no splicing effect.
BS1
Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00000827 (12/1450604) while in subpopulation EAS AF= 0.000278 (11/39602). AF 95% confidence interval is 0.000155. There are 0 homozygotes in gnomad4_exome. There are 5 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High AC in GnomAdExome4 at 12 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYPN | NM_032578.4 | c.1419T>C | p.Thr473Thr | synonymous_variant | 7/20 | ENST00000358913.10 | NP_115967.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYPN | ENST00000358913.10 | c.1419T>C | p.Thr473Thr | synonymous_variant | 7/20 | 1 | NM_032578.4 | ENSP00000351790.5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251040Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135670
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GnomAD4 exome AF: 0.00000827 AC: 12AN: 1450604Hom.: 0 Cov.: 29 AF XY: 0.00000692 AC XY: 5AN XY: 722316
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GnomAD4 genome Cov.: 32
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32
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3476
ClinVar
Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link
Submissions by phenotype
not provided Other:1
not provided, no classification provided | curation | Leiden Muscular Dystrophy (MYPN) | Apr 27, 2012 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
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