rs1057519573
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 16P and 4B. PVS1PP5_Very_StrongBS2
The NM_032578.4(MYPN):c.3214C>T(p.Arg1072Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_032578.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYPN | NM_032578.4 | c.3214C>T | p.Arg1072Ter | stop_gained | 16/20 | ENST00000358913.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYPN | ENST00000358913.10 | c.3214C>T | p.Arg1072Ter | stop_gained | 16/20 | 1 | NM_032578.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251366Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135846
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461732Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727172
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 08, 2022 | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28017374) - |
MYPN-related myopathy Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 16, 2024 | - - |
Dilated cardiomyopathy 1KK Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 16, 2020 | Loss-of-function variants in MYPN are known to be pathogenic (PMID: 28017374). For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with nemaline myopathy (PMID: 28017374). ClinVar contains an entry for this variant (Variation ID: 375568). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg1072*) in the MYPN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYPN are known to be pathogenic (PMID: 28017374). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at