rs548318517
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2
The NM_032578.4(MYPN):c.1952C>A(p.Pro651Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000057 in 1,613,998 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P651L) has been classified as Uncertain significance.
Frequency
Consequence
NM_032578.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYPN | NM_032578.4 | c.1952C>A | p.Pro651Gln | missense_variant | 10/20 | ENST00000358913.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYPN | ENST00000358913.10 | c.1952C>A | p.Pro651Gln | missense_variant | 10/20 | 1 | NM_032578.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152040Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000180 AC: 45AN: 250084Hom.: 1 AF XY: 0.000118 AC XY: 16AN XY: 135452
GnomAD4 exome AF: 0.0000513 AC: 75AN: 1461840Hom.: 1 Cov.: 34 AF XY: 0.0000454 AC XY: 33AN XY: 727220
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74382
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1KK Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 27, 2022 | This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 651 of the MYPN protein (p.Pro651Gln). This variant is present in population databases (rs548318517, gnomAD 0.1%), including at least one homozygous and/or hemizygous individual. 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: 477744). 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: "Tolerated"; 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 10, 2021 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 12, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at