rs201600440
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_032578.4(MYPN):c.3440T>A(p.Ile1147Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000886 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I1147T) has been classified as Uncertain significance.
Frequency
Consequence
NM_032578.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYPN | NM_032578.4 | c.3440T>A | p.Ile1147Asn | missense_variant | 17/20 | ENST00000358913.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYPN | ENST00000358913.10 | c.3440T>A | p.Ile1147Asn | missense_variant | 17/20 | 1 | NM_032578.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152152Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251450Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135894
GnomAD4 exome AF: 0.0000889 AC: 130AN: 1461884Hom.: 0 Cov.: 41 AF XY: 0.0000866 AC XY: 63AN XY: 727242
GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152152Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4AN XY: 74320
ClinVar
Submissions by phenotype
not provided Uncertain:4
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jan 14, 2020 | - - |
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | MYPN: PM2, BP4 - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 12, 2023 | Reported in one individual from a cohort of individuals not selected for cardiomyopathy, arrhythmia, or family history of sudden cardiac death, who underwent exome sequencing (PMID: 23861362); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26582918, 23861362) - |
Dilated cardiomyopathy 1KK Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 12, 2022 | This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 1147 of the MYPN protein (p.Ile1147Asn). This variant is present in population databases (rs201600440, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MYPN-related conditions. ClinVar contains an entry for this variant (Variation ID: 191758). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 29, 2022 | The p.I1147N variant (also known as c.3440T>A), located in coding exon 16 of the MYPN gene, results from a T to A substitution at nucleotide position 3440. The isoleucine at codon 1147 is replaced by asparagine, an amino acid with dissimilar properties. This alteration has been reported as a secondary cardiac variant in an exome cohort (Ng D et al. Circ Cardiovasc Genet, 2013 Aug;6:337-46). This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at