rs750655311
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BS1_SupportingBS2
The NM_032578.4(MYPN):c.3763G>A(p.Val1255Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000638 in 1,614,086 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1255G) 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 -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYPN | NM_032578.4 | c.3763G>A | p.Val1255Met | missense_variant | 19/20 | ENST00000358913.10 | |
LOC124902443 | XR_007062176.1 | n.128-2614C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYPN | ENST00000358913.10 | c.3763G>A | p.Val1255Met | missense_variant | 19/20 | 1 | NM_032578.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152204Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000557 AC: 14AN: 251188Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135742
GnomAD4 exome AF: 0.0000650 AC: 95AN: 1461882Hom.: 0 Cov.: 32 AF XY: 0.0000605 AC XY: 44AN XY: 727240
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152204Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74360
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 18, 2016 | The p.Val1255Met variant in MYPN has not been previously reported in individuals with cardiomyopathy, but has been identified in 2/11564 of Latino chromosomes b y the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs750655311). Computational prediction tools and conservation analysis do not pr ovide strong support for or against an impact to the protein. In summary, the cl inical significance of the p.Val1255Met variant is uncertain. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 15, 2022 | Reported in one Spanish patient with DCM (Pea-Pea et al., 2021); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32826072) - |
Dilated cardiomyopathy 1A Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute | Mar 15, 2019 | - - |
Dilated cardiomyopathy 1KK Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 16, 2022 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1255 of the MYPN protein (p.Val1255Met). This variant is present in population databases (rs750655311, gnomAD 0.02%). 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: 229036). 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: "Probably 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 | Jun 01, 2018 | The p.V1255M variant (also known as c.3763G>A), located in coding exon 18 of the MYPN gene, results from a G to A substitution at nucleotide position 3763. The valine at codon 1255 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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