rs1554845447
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_032578.4(MYPN):āc.1681T>Cā(p.Ser561Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. S561S) has been classified as Likely benign.
Frequency
Consequence
NM_032578.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYPN | NM_032578.4 | c.1681T>C | p.Ser561Pro | missense_variant | 10/20 | ENST00000358913.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYPN | ENST00000358913.10 | c.1681T>C | p.Ser561Pro | missense_variant | 10/20 | 1 | NM_032578.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 151902Hom.: 0 Cov.: 32 FAILED QC
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461794Hom.: 0 Cov.: 79 AF XY: 0.00 AC XY: 0AN XY: 727192
GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 151902Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74172
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1KK Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 20, 2022 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 520304). This variant has not been reported in the literature in individuals affected with MYPN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 561 of the MYPN protein (p.Ser561Pro). - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 03, 2019 | The p.S561P variant (also known as c.1681T>C), located in coding exon 9 of the MYPN gene, results from a T to C substitution at nucleotide position 1681. The serine at codon 561 is replaced by proline, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, proline is the reference amino acid in other 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